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". 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. 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, 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 obviously unsuited for such work. In actuality, Bartlett is really a Holocaust survivor who believes that one of the other workers may be a long-sought Nazi war criminal.
While motoring west, Tod and Buz encounter Lotti Montana, a fugitive accused of murder. When the boys inadvertently bring about Lotti's recapture by a vindictive sheriff, 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. However, they soon unexpectedly find themselves appointed as babysitters to Emerson's two spoiled and out of control children Curt and Karen. When Curt'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 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 and the models' chaperone were once wed to each other, and divorced under bitter circumstances.
Grizzled old prospector Jack McConkle 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 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 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 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, 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. 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. 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. 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. 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", 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, who sleepwalks through life, refusing to accept the reality of her husband's death. The chief pilot, Summers, 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, 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 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 who 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' 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, a notorious gambler, and Francis Oliver, 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 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, and her alcoholic uncle Mike. 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 runs his New Mexico cattle spread like a feudal baron. When his reckless son impregnates a young Indian girl, 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 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, 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 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, the other a mute servant girl.