Tod Stiles and Buz Murdock are two young men traveling across the backroads of America in search of adventure and fortune. When their corvette breaks down in the small community of Garth, Mississippi, the boys find themselves in a hostile town ruled by the despotic head citizen "Mr. Garth" (Everett Sloane). It seems the town of Garth is protecting some ugly secret, and trying to find out what that secret is may cost Tod and Buz their lives.
In Louisiana, Tod and Buz sign aboard the shrimp boat of captain Charlotte Duval (Janice Rule). They find themselves having to deal with their skipper's fierce independence, a jealous suitor and an approaching hurricane.
Tod and Buz arrive in swinging New Orleans. They make a date with a nice local girl named Carrie Purcell (Zina Bethune), unaware of the poverty the girl lives in or the adventures she is about to lead them into involving gangsters and a parrot fever epidemic sweeping the city.
Now working on an offshore drilling rig in the Louisiana gulf, Tod and Buz become curious about one of their coworkers - an elderly man named Bartlett (Lew Ayres) obviously unsuited for such work. In actuality, Bartlett is really a Holocaust survivor who believes that one of the other workers (Alfred Ryder) may be a long-sought Nazi war criminal.
While motoring west, Tod and Buz encounter Lotti Montana (Suzanne Pleshette), a fugitive accused of murder. When the boys inadvertently bring about Lotti's recapture by a vindictive sheriff (John Larch), they set out to clear her name.
The citizens of rural southwestern Utah fight a daily struggle against the harsh conditions of nature just to maintain the land they live on. A misguided act of kindness brings Tod and Buz into the lives of one such family, the Pages, consisting of three orphaned children. When a well malfunction leaves the Pages facing imminent drought, the boys lend the assistance of their corvette's motor to aid in the repairs. But the remorseless conditions of the inhospitable climate threaten to make their task hopeless.
Tod and Buz arrive in the sleepy coastal town of Grants Pass, Oregon, where they hook on as workers with local hop farmer Gerald Emerson (E.G. Marshall). However, they soon unexpectedly find themselves appointed as babysitters to Emerson's two spoiled and out of control children Curt (Stephen Bolster) and Karen (Joey Heatherton). When Stephen's irresponsibility costs the lives of one of the workers, our two heroes find themselves the only people in town who will work for the Emersons and must bring the situation to rights.
Making the journey all the way from her native Italy to the Pacific Northwest, Lucia Trapani (Arlene Sax) has come on a holy mission. She has arrived to claim her inheritance to fund the purchase of a Madonna statue for her village church. Unfortunately, her "heritage" is a bogus promise bequeathed her years ago by a well-meaning but imaginative American soldier during World War II - who told Lucia he held the deed to the entire state of Oregon! It's up to Tod and Buz to protect the young woman from disillusionment and find a way for her to fulfill her quest.
Working as members of the construction crew on Glen Canyon Dam in Arizona, Tod and Buz are pulled for special duty - to act as bodyguards for a quartet of young fashion models being flown in for a photo shoot on the site. Our two young adventurers suddenly find themselves the sole bulwark between the models and a town full of single construction workers. Further complicating matters is the fact that the construction foreman (Charles McGraw) and the models' chaperone (Bethel Leslie) were once wed to each other, and divorced under bitter circumstances.
Grizzled old prospector Jack McConkle (Edgar Buchanan) has finally hit upon the strike of a lifetime - discovering a vein of rare Beryllium ore in the desert of the American southwest. However, Tod and Buz's employer, land baron Durant (Edward Binns) is bent on bullying the old man into relinquishing his claim upon the find. To the rescue come Tod and Buz, determined to protect McConkle's interests. But they are about to find that Durant plays hardball, and their own lives are imperiled by their involvement.
Officials at Carlsbad Caverns National Park are flabbergasted when renown scientist Mark Christopher (Leslie Neilsen) brings a convoy of families and animals into the caves with every intention of settling down. It seems that Christopher is in possession of information that leads him to believe that Russia is shortly planning to launch a nuclear attack on the US, and he has brought his ragtag group to the caverns in an attempt to survive the holocaust he believes is imminent. Tod and Buz are drawn into the compelling story, and hold their breath along with the rest of the nation as the appointed hour of doom approaches . . .
In El Paso, Texas, Laura Church (Whitney Blake) has just been released from a stay in prison, convicted of an embezzlement she was not guilty of. But her parole officer is none other than local big shot Woody Biggs (Lee Marvin), the man who framed her in the first place, the man who caused the death of her ex-husband, the man who now has designs on her from which escape seems futile.
Laura's situation seems hopeless. But little does she know that two knight errants have rode into town in the persons of Tod Stiles and Buz Murdock.
Racing fever grips Tod as he lives out a lifelong fantasy to become a race car driver when he is asked to relieve one of the entries in the Grand Prix at Riverside. During preperation for the race, Tod begins to fall for his patron's stepdaughter (Susan Kohner). But Buz has suspicions that the young woman is just using Tod, attempting to keep him from entering the race for her own purposes.
Tooling around the hot spots of Southern California, Tod and Buz are treated to a performance by jazz trumpet legend Gabe Johnson (Jack Lord). However, on the way back from the show, they come to the aid of a crashed motorist , a distraught woman who turns out to be none other than Gabe's wife Jana (Anne Francis). Jana claims that her husband is an unstable personality who is trying to kill her.
On the ranch lands of Southern California, Tod and Buz encounter the latest character in their cross-country travels: date rancher Adam Darcey (Jack Warden). The invalid Darcey is in mortal combat with the State Highway Department, who wants to build a new road through his property. Darcey keeps vigil on his front porch with a rifle to prevent construction work. Secretly, he is in love with his lovely young ward "Sweet Thing" (Anne Helm), the apple of the eye of every young man in town.
Tod and Buz motor into Pheonix, Arizona. Tod is thrilled at the prospect of going to work as a prospector for Jack Windus, the man who first taught Tod how to fly. However, when he arrives at the cropdusting outfit, Tod learns that Windus is dead. The business is now run by his wife Dora (Cathy Lewis), who sleepwalks through life, refusing to accept the reality of her husband's death. The chief pilot, Summers (Michael Rennie), is a brooding depressive convinced that he will bring death and ruin into the life of anyone he is involved with. He attempts to avoid all personal entanglements, including that of his wife Christina (Dorothy Malone), who is hopelessly devoted to him. Tod seeks to convince the reclusive Summers to take him on as an apprentice, while Buz meanwhile begins to fall for Christina . . .
Tod's aspiration to become a cropdusting pilot has led him and Buz into a complex situation involving the interrelationships of the people concerned with the Windus crop dusting company. Tod has succesfully petitioned for the comapny's head pilot Summers (Michael Rennie) to teach him the ropes of the business despite the latter man's reluctance. The financially strapped company is offered a dangerous contract requiring the plane to carry a hazardous load of sulpher. The dramatic events that subsequently unfold make for one of Tod and Buz's most unforgettable experiences in this epic two-parter.
Tod and Buz encounter a bored poor little rich girl from Hollywood (Patty McCormack) attempts to spice up her life by pretending to be the target of mobster kidnappers. Her concerned parents have hired a private detective agency in an attempt to track the girl down. With our heroes and the gumshoes each believing the others to be the bad guys, hilarity is sure to ensure in this example of lighter fare from Route 66's first season.
When Donna Stevens' (Martha Hyer) husband is murdered, the small-time crooks spare her life because of her blindness. Now, she is determined not to let the handicap that saved her prevent her from single-handedly finding her husband's killers and avenging herself upon them - and her plans invlolve an unwitting Tod and Buz.
Is this the end of a partnership? Tod and Buz part ways when Tod returns a runaway boy to an orphanage. Buz, with his own unpleasant memories of such institutions, strikes out on his own as a protest to Tod's decision. Later, working for a livestock auction, Buz encounters an older woman, matron of a group of traveling female entertainers, who once gave up her young son and the two become drawn to each other. Before the end of this story, Tod and Buz will come to blows before reconciling.
Tod and Buz are working at the exclusive Squaw Valley ski resort in central California. A serial killer preying on young women is prowling the resort.
On the road to Reno, Tod and Buz meet up with Sam Keep (Walter Matthau), a notorious gambler, and Francis Oliver (Ed Andrews), the financier assigned to keep him in line. The folks of a tiny Nevada town have sent the two on a gambling mission in a desperate attempt to acquire the funds needed to save it. The plan threatens to go awry when the normally staid and conservative Oliver catches gambling fever.
Summoned to his aunt Kitty's (Beatrice Straight) deathbed in the slums of Los Angeles, Tod is given a desperate request - to locate her missing daughter Carol, Tod's cousin. Tod's search for the young girl will not only take him through the seediness and violence of life on the wrong side of the tracks - including involving him and Buz in a brutal brawl with a street gang - but will also force him to confront the dark side of his own personality, in one of the grimmest offerings of Route 66's first season.
In San Diego, Tod and Buz become drawn into the lives of preocious nine-year old heiress Linda McKay (Susan Melvin), and her alcoholic uncle Mike (Dan Duryea). When Mike's irresponsible behavior threatens to cause him to lose custody of his beloved niece, Tod and Buz step in in an attempt to shape the man up and salvage the situation. But neither them nor Linda is aware of the secret Mike is harboring.
Frank Ivy (Albert Dekker) runs his New Mexico cattle spread like a feudal baron. When his reckless son impregnates a young Indian girl (Arlene Sax), and then dies in an accident, Ivy kidnaps the young woman and brings her to his estate to raise the child as his own, against the woman's wishes. But among Ivy's ranch hands are employed Tod and Buz, who aid the girl in escaping and in a subsequent attempt to get her to refuge and sanctuary on a reservation. But our two young adventurers soon learn that they will not arrive without first facing one of their most difficult challenges - delivering a baby.
When Tod and Buz prevent New Mexico sportsman "Hump" Humphrey (Gene Evans) from poaching a doe, they soon learn that the hunter is a borderline psychotic personality - and that he now has his sights set on the duo.
When Tod and Buz stop to aid what appears to be a stranded motorist in rural New Mexico, the duo finds themselves kidnapped. The reason? They've been recruited as schoolteachers in the tiny villa of Cordova. You see, Cordova has no teachers of its own, and fears that the closing of the schools will imperil the survival of the very community.
In Youngstown, Ohio, Buz looks forward to a reunion with his boyhood idol, former boxing great Johnny Copa (Darren McGavin), who is participating in a bout in the city. However, Buz is distraught to find that Copa's career has hit the skids, and that he has been reduced to the status of second-billing punching fodder for up and coming contenders. Buz takes a position in Johnny's corner the night of the bout, determined to help the fighter taste victory once again.
Tod and Buz are working in the tiny hamlet of Amity, Ohio, when native daughter Joan Maslow (Susan Oliver) returns to town. The boys try to aid her in the seemingly innocuous task of moving her late mother's body from a potter's field into the town cemetery. They are astonished when the people of Amity violently oppose the move.
The series concludes a succesful first season with a classic offering set in Cleveland, Ohio - as Tod and Buz become involved in a touching love story featuring two misfits. One a simian construction laborer (Nehemiah Persoff), the other a mute servant girl (Lois Smith).
Broadway sensation Arlene Sims (Anne Francis) suddenly breaks off her career to return to her hometown of Butte, Montana. Arlene is dying of a rare disease and has come home to spend her final days. But she didn't count on meeting Buz Murdock, who becomes smitten with her. As their relationship grows, Buz contemplates marriage, blissfully unaware that Arelene's time is running out.
To save the life of a wild stallion named "Blue Murder", who has been determined to be too dangerous to be allowed to live, Tod and Buz pledge to personally deliver the horse to rancher Jim Bludge (Gene Evans) in rural Montana. But when Bludge is found trampled to death, Tod is wracked with guilt and vows to hunt down and kill the animal himself.
In Pittsburgh, Tod and Buz befriend ailing elderly former blues singer Jennie Henderson (Ethel Waters). They then set out to fulfill Jennie's dying request: to reunite the members of her old combo for one final performance.
On the streets of Boston, Tod and Buz encounter Arnie (Robert Duvall) - a heroin addict in the throes of withdrawal. Tod wants to help the man. However Buz, who has had one too many experiences with junkies in his past, vehemently disagrees - Arnie's case is hopeless, he says, and not worth their time. Tod is puzzled at his usually altruistic close friend's sudden coldness, and wonders at its real cause.
Once again in Cleveland, Tod and Buz become part of the Polish blue collar community. Their boss Jack Kolodziedjczak's (Nehemiah Persoff) greatest pride is his son Janosh (Robert Redford), whom he is grooming to be a doctor. But tragedy strikes when Janosh's girlfriend Terry (Ann Dee), the daughter of Jack's best friend Mike Palinski (Martin Balsam) is found dead at the bottom of a ravine. With Janosh on the lam, Jack vows to avenge Terry's death, even if it means killing his own beloved son.
Tod and Buz are working in the Adams shipyards in Massachusetts. With the sudden death of the owner, socialite and heiress Prudence Adams (Janice Rule) arrives for the funeral and to take charge of her father's business. A romance develops between Tod and Prudence, which develops into something serious very quickly. Are there wedding bells in Tod's future?
All his life, Buz has wondered about the mother who abandoned him when he was an infant to live out an orphaned childhood. Now in the small town of Hester, Maryland, Buz has discovered a family - the Colbys - who look like they could be his brothers and sisters. With Tod and a tiny faded photograph, Buz starts on a quest through the streets of Baltimore to find the woman who may be his real mother.
Lillian Aldrich (Nina Foch) is trying to fit back into society after spending the last eighteen years in a mental hospital. On her first day back at work, she gets into an argument with Buz, who is unaware of her condition. When Lillian flees the office in tears, Tod and Buz learn of the situation. They resolve to help Lillian in her readjustment to normal life and to seek out the daughter who believes her to be dead.
In Pittsburgh, Tod finds himself enamored of lounge singer Perette Dijon (Macha Meril). However, Perette is a beautiful princess locked up in a tower - the Mariott Hotel overlooking the city - and the dragon who guards her is her intensely jealous and possessive manager Glenn Ryan (Lee Marvin). When Tod attempts to court Perette, Ryan knocks him cold with a karate chop. Tod vows revenge and plans for a final showdown with Ryan in his aerie.
In Carlisle, Pennsylvania, Tod and Buz encounter traveling beauty contest promoter Max Coyne (Keenan Wynn) and are enlisted by him to help stage his latest competition in that town. However, when the community leans that Coyne is a fraud and a con man, our two young heroes may wind up in jail along with him.
Tod and Buz attend a party at a Philadelphia hotel. A misguided prank pulled by a pair of college boys results in Tod drinking a beer that has been spiked with a powerful, experimental hallucinogen. Tod flees the hotel and goes on a one-man rampage through the city as the effects of the drug cause him to experience extreme emotions and sensations: fear, rage, elation, paranoia. Buz and the Philadelphia police force must find Tod before the final phase of the drug takes place - Tod will enter a state of extreme depression in which it is certain he will attempt to take his own life.
In Philadelphia, Tod and Buz pay a visit to Chuck Brennan (Milt Kamen), a social worker who was instrumental in helping Buz escape a life of juvenile delinquincy as a youth. Brennan continues to work with street gangs, and accepts the challenge of a local gang leader named Packy (Martin Sheen) to a dare game played on the rooftops of the city's apartment buildings. Brennan is killed during the contest, and it falls on Tod, Buz and the gang's reformed former leader Johnny (James Cann) to bring down Packy.
In rural Pennsylvania, Tod and Buz work for the Bracks, a wealthy family led by the domineering widow Agnes (Beulah Bondi). Another widow enters the picture, Agnes' daughter-in-law Julie (Inger Stevens), who comes overseas from Europe bearing Agnes' grandson. When the family treats her arrival with open coldness and hostility, Tod and Buz are left as the only ones in town who seem willing to offer the young woman hospitality.
Touring historical monuments in Boston, Tod and Buz meet John Westerbrook (Dan O'Herlihy), an eccentric yet distinguished man who displays a strong patriotism and travels with a small contingent of bodyguards. The boys later learn that Westerbrook is the head of a white supremacist organization. Boston police enlist the aid of our two leads, as Tod works inside the organization and Buz outside. The race is against time, as Westerbrook's organization seems about to be planning something which will result in the deaths of many innoncents.
Tod and Buz pick up work when the traveling rodeo comes to Mesquite, Texas. They come to the rescue of rodeo clown Ollie Crump (Albert Salmi) from hazing at the hands of the outfits cowboys. Ollie is a former rider whose injury has led him to become a clown, and nurses a secret love for alcoholic trick rider Babe Hunter (Audrey Totter).
Framed for a crime he didn't commit, David Job (John Ericson) returns home to his small Texas town following a five-year prison stint. He takes complete control of the town and kidnaps lead citizen Bob Harcourt (DeForest Kelley), the man responsible for his frame-up. David intends to convene a kangaroo court in the local courthouse to pass judgement on Harcourt. Among the enforced participants in the trial are passerbys Tod and Buz.
Tod and Buz are working at a Long Beach veterans hospital. This brings them into the life of Frank Madera (Steven Hill) a paraplegic who has been embittered ever since his wife left him, and Lori Barton (Bethel Leslie), the nurse who loves him.
Tod and Buz arrive in Tucson, Arizona, at the same time as Vicki Russell (Julie Newmar), a free-spirited motorcyclist. Vicki manages to get herself tossed in jail within minutes of coming to town. Buz is fascinated by the young girl's cavalier approach to life and existence and springs for her bail, against Tod's better judgement. However, it is Tod who later falls under Vicki's spell and goes on a joyride with her into the Arizona desert.
In Dallas, Buz is kidnapped by Caine (David Wayne), a religious fanatic who has left a trail of dead bodies across the major cities of the United States. Caine wants the entire city to abstain from sin for twenty-four hours . . . or else Buz will become his latest victim.
Tod and Buz are working as day laborers for a Scottsdale, Arizona, development firm. When the company seeks a new vice president, Terry Prentiss (Patricia Barry) promotes Buz to that executive position as part of a power play to demonstrate to her boss Lee Fisk (Peter Graves) that a woman can be a corporate executive. Buz, suddenly finding himself in high-rolling executive boardroom meetings, becomes Terry's puppet in this comedy of errors.
In Phoenix, Tod and Buz befriend their employer Carl Selman (Ed Asner). When Carl is killed in a senseless mugging, the boys must come to the emotional rescue of his young son Davey (Mike McGreevey), who has a crisis of faith on the verge of his Bar Mitzvah.
When he was an undergraduate at Yale, Tod had a crush on a dancer named Rosemarie Brown (Elizabeth Seal). Years later, Rosemarie has fallen on hard times, having just been widowed by an alcoholic husband. Tod and Buz, working for a Hollywood TV station, urge Rosemarie to audition for a dance troupe for one of their shows as a means to get her back on her feet.
Tod is hired for a special assignment - to be the special assistant to speed boat motor designer Sandy Mason (John Larch). The demands of this driven man who is on the verge of a revolutionary breakthrough in engine design keep Tod working overtime. But when Mason's prodigal daughter (Lois Smith) arrives on the scene, Tod finds himself drawn just as intensely into the man's personal life as well as his professional.
Buz is knocked out during a construction work accident, and when he regains consciousness he finds that he is unable to see! A doctor tells him his loss of vision may be temporary, or it may be permanent. Buz first contemplates taking his own life, but then agrees to enroll in a Texas institute for the blind so that he can retrain himself to live in society. Buz is assigned a young blind woman (Barbara Barrie) as his teacher, and as he gradually begins to cope with both his blindness and becoming part of the world again he begins to fall in love with the young woman. This episode marks one of George Maharis' most memorable performances of the series.
Tod and Buz are stopping over for lunch in a sleepy little Texas town. Suddenly, a bus pulls into town, and one of the passengers who disembarks is a young woman (Tuesday Weld) who is wearing a hideously frightful mask. The girl's purpose for arriving thus costumed seems to be part of a mysterious vedetta against the town. Unable to resist the lure of this mystery, Tod and Buz attempt to gain the confidence of the woman to find out who she is and the purpose behind her arrival.
After stopping to help a young woman (Zina Bethune) with car trouble, Tod and Buz find themselves part of a kidnapping. They soon learn that the woman is the daughter of famed embezzler and international fugitive Charles Clayton (Douglas Fairbanks, Jr.). Clayton has risked recapture to come back to the United States to visit his daughter.
While working as deckhands on a Cleveland river tour ferry, Tod and Buz come to the rescue when a young boy goes off the boat into the water. The boy, Richie McIntyre (Brad Herrman) turns out to be the son of local business tycoon Willard McIntyre (Ralph Meeker), and claims that he did not fall overboard, but was pushed. Then the elder Mcintyre begins receiving threatening notes intimating at a kidnapping of his son, and then Richie disappears . . .
Tod and Buz, themselves under suspicion, go on a hunt for the boy in an attempt to solve the mystery.
A Jet-setter named Lola (Joanna Moore), bored with her rich life, dives overboard the side of her luxury boat and swims for the shore of California's Catalina Island in search of adventure. What she finds is Buz Murdock, working alone on the island, and astonished to see the woman walk towards him out of the water like an incarnation of Aphrodite.
Buz and Lola begin to flirt with each other; but their games soon turn serious when Lola, wandering the beach, manages to get her foot stuck in the rocks in a cove. The high tide is coming in, meaning that the girl could drown in her predicament.
Buz is unable to free the woman without assistance. But Tod has gone to the mainland for supplies, and the resort community is deserted for the off-season. As the waves mount higher and higher the plight of the trapped girl becomes more and more dire as Buz desperately searches for a way to free her or get help.
With Buz laid up in the hospital, Tod is left to work double duty for the duo at the Venice Beach amusement park. One night at a bar, he meets Cris Sinclair (Susan Oliver), an impulsive and exciting young blonde woman . The next day at work, he is approached by her sister, the reserved and bespectcled Claire, who warns Tod that involvement with Cris may spell disaster for both of them.
Tod enters the world of professional wrestling as he goes to work for a promoter of the "sport". Tod's boss has financed the release of a longtime Hungarian political prisoner named Sandor (Jack Warden) in order to bring him to the United States to add to his stable of wrestlers. The proud Sandor, accustomed to traditional wrestling, is about to learn what it means to be involved in the Americanized version, where staging and showmanship trump strength and skill.
Tod and Buz are in Chicago, Tod as a taxi driver, who picks up a former prohibition gangster, who thinks someone from his past is out to kill him.
Horror legends Boris Karloff, Lon Chaney, Jr., and Peter Lorre portray themselves as they travel to a hotel in Chicago in order to find out if the old monsters can still scare a modern day audience.
Tod is kidnapped by a convicted murderer while waiting at a railroad station for a bridesmaid.
Tod and Buz pick up a young German who has jumped ship in order to find the man to be his father in order to kill him.
Tod joins with a posse looking for a pair of killers.
Tod meets a man named Lincoln Case, a Green Beret who has returned home from Vietnam, and becomes Tod's new traveling companion.
Tod and Linc are working at Florida's Wikkee Watchee theme park, where Tod meets a young lady who claims to be a real mermaid.
Tod and Linc get involved in helping two Cuban refugee brothers get their niece out of Cuba.
Tod and Linc visit Linc's former commanding officer from Vietnam who, because of a combat injury to the head, has the mentality of an eight-year-old.
While walking to a gas station to get fuel for Tod's Corvette, Linc is kidnapped by two men on their way to a wedding.
Linc is falsely accused of injuring a dog in the neighborhood where he is working.
While visiting Toronto in the Dominion of Canada, Tod and Linc try to help a stranded all girl jazz band get back to St. Louis.
Tired of their parent's quarreling, a two children take their baby brother and set up their own household.
Linc crosses paths with a former soldier from his unit in Vietnam who was responsible for the men in Linc's unit getting killed.
A teenager holds Tod and Linc hostage after accidentally killing a policeman.
Tod is kidnapped by a political assassin who is his exact double.