| • Mike Barker (1) | voiced | Delivery Man / Terry Bates / Gordon / Various / Flower / Biology Teacher / Mannie / Chuck White / Jesus / Sanders / Jerry / Meter Maid / Scientist / Nick / Frank / Jock #2 | Pig / Terry Bates | Ticket Guy | Valet / Terry Bates | Contestant / Terry Bates | Mr. Madsen / Terry Bates | Agent Mulder / Terry Bates | Deer | Dr. Heisler / Terry Bates | Chuck White / Sanders | Ron / Mugger / Zargon Cult Member #1 / Cashier / Security Guard / Tyler Johnson / CIA Lab Tech / Stone Mayhem Announcer | 84 Episodes |
| • Curtis Armstrong | voiced | Schmuley “Snot” Lonstein | 60 Episodes |
| • Patrick Stewart | voiced | Bullock / Avery Bullock | 55 Episodes |
| • Eddie Kaye Thomas | voiced | Barry / Barry Robinson / Flandnag / Barry Robinson | Spike Baltar | 48 Episodes |
| • Jeff Fischer (1) | voiced | Jeff Fischer / Jeff Fischer | Donnie Patterson / Various | 40 Episodes |
| • Kevin Michael Richardson | voiced | TV Announcer / Principal Lewis / Principal Brian Lewis / Various / Big Monty / Principal Brian Lewis | TV Announcer / Jerry / Tank Bates / Tow Truck Driver / Vitas / Theater Sweeper / Black Villian | 39 Episodes |
| • Daisuke Suzuki | voiced | Toshi Hirano / Popo / Asian Man | 39 Episodes |
| • Erik Durbin | voiced | Reginald / Manny / Various / Gerald / Langley Falls Town Geologist / The DJ / Crack Head BooBoo / Janitor / Randy / Zargon Cult Member #2 / Bob Todd / Philippe Monday / Lil' Turtle | 36 Episodes |
| • Matt McKenna | voiced | Buckle / Disability Check Dan / Captain Monte / Mr. Stashwick / Various / Bailliff / Jesus / Drill Sergeant / Coach Andrews / Coach Patterson / Cap'n Monty | Kevin Broham / Unknown / Zargon Cult Leader / Ghoul / Santa / Homeless Guy #3 | 32 Episodes |
| • Mike Henry (1) | voiced | Jackson / Senator #2 / Taco / Bee / Gang Leader / Various / Jackson | Maitre D' / Faziz / Jackson | Michael Moore | Faziz / Jackson | Painter / Jackson | Taco King / Kayaker / Jackson | Strip Club Patron / Jackson's Hooker / Cleveland Brown | 30 Episodes |
| • Alex Cuthbertson | voiced | Kid / Various / Joel Larson | 21 Episodes |
| • Jonathan Fener | voiced | Airline Steward / Various / Inmate / Helicopter Perry | 20 Episodes |
| • Seth MacFarlane | voiced | Greg Corbin / Greg Corbin | Film Narrator / Peter Griffin / Brian Griffin / Stewie Griffin / Glenn Quagmire / Strip Club Patron / Kevin Rowland | 18 Episodes |
| • André Sogliuzzo | voiced | Teacher / Johnny Depp / Various / Dill / George Clooney / Deaf Teddy | Blind Jimmy / Manager / Gabe Kaplan / Spy / Young Father | 16 Episodes |
| • Chris Diamantopoulos | voiced | Donald Sutherland / Robert Deniro / Various / Sander's Double / Hanson Foam Man / Senor Hidalgo / Delorean Door Owner / Scott / Alejandro | 15 Episodes |
| • Paget Brewster | voiced | Judy / Michelle / Michelle Morris / Unknown / Raina Markovitz / Casey / Thundercat / Mia / Carmen Selectra / Shapeshifter | 15 Episodes |
| • David Koechner | voiced | Dick Reynolds / Unknown | 14 Episodes |
| • Laura McCreary | voiced | Various / Stewardess / Unknown / Helen / Old Lady Singer / Jenny Johnson | 11 Episodes |
| • Fred Tatasciore | voiced | Various / Bill Elliot / Senator / Warden / Johnny Four-Legs / Police of Vice & Virtue #2 | Judge / Police of Vice & Virtue #2 / League Official / Lieutenant Goldberg | 11 Episodes |
| • Matt E. Mixer | voiced | Various | 11 Episodes |
| • Martin Mull | voiced | Father Donovan | 10 Episodes |
| • Stephen Root | voiced | Dick / Dentist's Father / Dick Reynolds | Co-Worker #4 / Dick Reynolds | 10 Episodes |
| • Jill Talley | voiced | Cocktail Waitress / Flight Attendant / Oscar's Mother / Various / Senator Feinstein | Maria / Fat Lady / Janet Gustafson / Little Girl's Mom | Ramona / Dalia / Workshop Representative | 10 Episodes |
| • Erik Sommers | voiced | Various / Rivers | 10 Episodes |
| • John DiMaggio | voiced | Sergei Petkov / Car Repo Guy / Priest / Brad, Leon / Bouncer | The Dove / Various / Sully / Hitman | 9 Episodes |
| • Matt Fusfeld | voiced | Various / Majestic | 9 Episodes |
| • Judah Miller | voiced | Various | 8 Episodes |
| • Rachael MacFarlane | voiced | Barbara "Barb" Hanson / Judy Panowitz / Sandy / Barbra Streisand / Gypsy / Cute Baby Pics Employee / Gertie / Nurse | 8 Episodes |
| • Amir Talai | voiced | Sanjay Bhudapar / Achmed Asadi / Various / Snake | 8 Episodes |
| • Eric Edwards | voiced | Bagel Shop Owner / Henry Callaway / Various / Manager / Nathan / Trevor | 8 Episodes |
| • Murray Miller | voiced | Unknown / Antichrist / Various | 7 Episodes |
| • Peter MacKenzie | voiced | Dr. Grossbard / Senator #1 / Various / Unknown / Chief Shopaholic | Midnight Runner #1 | Salesman / Dr. Grossbard | Senator #1 / Nathan's Dad / Mr. Chimdale | 7 Episodes |
| • Steve Hely | voiced | Jim Henson / Frank / Wolverine Player / Sergei Kruglov / Various | 7 Episodes |
| • Dee Bradley Baker | voiced | Grandpa Smith / Waiter / Coach Keegan / Kisses | Enormous Sea Monster / NGA Land Announcer / Little Tex | 6 Episodes |
| • Lisa Edelstein | voiced | Sharri Rothberg | 6 Episodes |
| • David Herman | voiced | Zack / Man / Various / Arboreus | Mr. Aids | 5 Episodes |
| • Will Forte | voiced | Fake Jesus / Mayor Woodside / Various / Security Officer | 5 Episodes |
| • Amy Hill | voiced | Mah Mah Ling | 5 Episodes |
| • Marissa Jaret Winokur | voiced | Various / Ugly Girl / Jewel | 5 Episodes |
| • J. B. Smoove | voiced | Airport Security Guard / Tracy Bryant / Various | 5 Episodes |
| • Niecy Nash | voiced | Patty Labelle / Angel / Lorraine | 5 Episodes |
| • Swoosie Kurtz | voiced | Marilyn / Betty Smith | 5 Episodes |
| • Sandra Oh | voiced | Mrs. Hirano / Katie | 5 Episodes |
| • Megyn Price | voiced | Linda Memari | 5 Episodes |
| • Scott Lowell | voiced | Felix / Brett / Barney / Various | 5 Episodes |
| • Leisha Hailey | voiced | Lily / Various | 5 Episodes |
| • Ari Graynor | voiced | Unknown / Various | 5 Episodes |
| • Nick Kroll | voiced | Various / Dry Cleaner | 5 Episodes |
| • Jane Lynch | voiced | Al / ObGyn Doctor / Unknown | 4 Episodes |
| • Wendy Schaal | voiced | Delta Burke / Bernie's Mom / Mom / Patricia | 4 Episodes |
| • Gregory Jbara | voiced | Plastic Surgeon / Brad Johnson / Unknown | 4 Episodes |
| • Scott Grimes | voiced | Blind Man / Photographer / Glass Guy #1 / Clay Aiken | 4 Episodes |
| • Richard Kind | voiced | Al Tuttle | 4 Episodes |
| • Nahnatchka Khan | voiced | Various | 4 Episodes |
| • Bob Odenkirk | voiced | Third Worker / TV Host / Mark / Various | 4 Episodes |
| • Richard Gant | voiced | Various / Firefighter | 4 Episodes |
| • Daran Norris | voiced | Jack Smith | 4 Episodes |
| • Donald Fullilove | voiced | The Cop / Reginald | 4 Episodes |
| • Lizzy Caplan | voiced | Debbie | 4 Episodes |
| • Peter Paige | voiced | Jason / Evan / Bouncer / Various | 4 Episodes |
| • Neal Feinberg | voiced | Khalid | Zacharias | Irv Rosenblath / Khalid / Unknown | 4 Episodes |
| • Rob Riggle | voiced | Harvey Lisle / Vic / Malcolm Hathaway / Various | 4 Episodes |
| • Travis Bowe | voiced | Ranch Hand / Various / Paramedic | 4 Episodes |
| • Paige King | voiced | Airline Employee / Various | 4 Episodes |
| • Tom Hollander | voiced | Waiter | Performance Artist / Amazing Rufus / Phil | 3 Episodes |
| • Clancy Brown | voiced | Henry Fischer / Various / Convenience Store Clerk | 3 Episodes |
| • Shawn Michael Howard (1) | voiced | Homeless Man / Various / Belmonpan | 3 Episodes |
| • Jon Tenney | voiced | Lawyer #2 / Father Carrington / Norman | 3 Episodes |
| • Molly Shannon | voiced | Christie White | 3 Episodes |
| • Seth Green | voiced | Etan Cohen / Matthew McConaughey / Joey | 3 Episodes |
| • Victor Raider-Wexler | voiced | Ray | 3 Episodes |
| • J. K. Simmons | voiced | The Judge / Various / Mr. McCreary | 3 Episodes |
| • Ron Livingston | voiced | Bob Memari | 3 Episodes |
| • Robert Tinkler | voiced | Clerk / Doyle / Various | 3 Episodes |
| • John Cho | voiced | Vince Chung | 3 Episodes |
| • Ivana Milicevic | voiced | Svetlana / Austrian Woman / Various | 3 Episodes |
| • Karen Maruyama | voiced | Kichiro / Cocoa / Woman | 3 Episodes |
| • Elizabeth Banks | voiced | Becky Arangino / Lisa Silver | 3 Episodes |
| • Forest Whitaker | voiced | Ron Turlington | 3 Episodes |
| • Don Tai | voiced | Qui Lo | 3 Episodes |
| • John Viener | voiced | Various | 3 Episodes |
| • Susie Essman | voiced | Unknown / Snot's Mom | 3 Episodes |
| • Amy Sedaris | voiced | Dr. Meg Penner / Dr. Lizzy / Various | 3 Episodes |
| • Ken Jeong | voiced | Dr. Perlmutter / Butch Johnson | 3 Episodes |
| • Rolando Molina | voiced | Mex | 3 Episodes |
| • Alan R. Cohen | voiced | Various | 3 Episodes |
| • Charles Dennis | voiced | Michael / Unknown | 3 Episodes |
| • Timothy Taule | voiced | Unknown / Blonde Spy | 3 Episodes |
| • Rick Podell | voiced | Various | 3 Episodes |
| • Brian Lally | voiced | Nebraska Man / Amy's Father / Art Teacher | 3 Episodes |
| • Michael Dunn (2) | voiced | Guard / Paramedic / Unknown | 3 Episodes |
| • Kamilah Marshall | voiced | Hershey Park Singer / Unknown | 3 Episodes |
| • Asa Taccone | voiced | Various | 3 Episodes |
| • Tim Kelleher | voiced | Unknown | 2 Episodes |
| • Tzi Ma | voiced | Bah Bah Ling | 2 Episodes |
| • Bryan Cranston | voiced | Mr. Winthrop / Bill Publisherman | 2 Episodes |
| • Reggie Lee | voiced | Mr. Hirano / Various | 2 Episodes |
| • Michael Pena | voiced | Margaritte | 2 Episodes |
| • Marianne Muellerleile | voiced | Augustus' Mother / Unknown | 2 Episodes |
| • Phill Lewis | voiced | Duper | 2 Episodes |
| • Raven-Symone | voiced | Katie / Woman | 2 Episodes |
| • Edward Asner | voiced | Grandpa Smith / Red Mailbox | 2 Episodes |
| • Zuhair Haddad | voiced | Old Man | Police of Vice & Virtue #3 / Various | 2 Episodes |
| • Elon Gold | voiced | Various | 2 Episodes |
| • Gina Gershon | voiced | American Girl #1 / Karen | 2 Episodes |
| • Sarah Michelle Gellar | voiced | Phyllis / Jenny | 2 Episodes |
| • Jodi Long | voiced | Trung's Mom / Various | 2 Episodes |
| • Missi Pyle | voiced | Various | 2 Episodes |
| • Beau Bridges | voiced | Lieutenant Thacker / Doctor | 2 Episodes |
| • Kathy Griffin | voiced | Kelly / Herself | 2 Episodes |
| • David Hemingson | voiced | Bartender / Hercules | 2 Episodes |
| • Brian Posehn | voiced | Dan Vebber | 2 Episodes |
| • Catero Colbert | voiced | Derek Jeter | 2 Episodes |
| • Jon Ross | voiced | Alien Man / Kurt | 2 Episodes |
| • Becki Newton | voiced | Unknown | 2 Episodes |
| • Grace Park | voiced | Akiko Yoshida | 2 Episodes |
| • James Patrick Stuart | voiced | Eddie / Various | 2 Episodes |
| • Alyson Hannigan | voiced | Chelsey / Herself | 2 Episodes |
| • D. D. Howard | voiced | Sheila | 2 Episodes |
| • Patton Oswalt | voiced | Bob / Ticket Taker | 2 Episodes |
| • Emmanuelle Chriqui | voiced | Unknown | 2 Episodes |
| • John Ennis | voiced | Tex | 2 Episodes |
| • Alan Tudyk | voiced | Various | 2 Episodes |
| • Azura Skye | voiced | Veronica / Various | 2 Episodes |
| • Wayne Brady | voiced | Tungee / Cuba Gooding Jr. | 2 Episodes |
| • Grey Delisle | voiced | Akiko | 2 Episodes |
| • Ron Perlman | voiced | Various / Colonel | 2 Episodes |
| • Jay Thomas | voiced | Brett Morris | 2 Episodes |
| • Jon Cryer | voiced | Quacky / Chimdale Desk Clerk | 2 Episodes |
| • Jenny Lewis (1) | voiced | Various | 2 Episodes |
| • Leslie Jordan | voiced | Mr. Beauregard | 2 Episodes |
| • Scott Mosenson (1) | voiced | Various | 2 Episodes |
| • Michelle Krusiec | voiced | Nurse / Hooker / Various | 2 Episodes |
| • Kat Dennings | voiced | Tanquarei / Various | 2 Episodes |
| • Ellen Albertini Dow | voiced | Woman on Bus / Old Woman | 2 Episodes |
| • Nathan Fillion | voiced | Liver / Various | 2 Episodes |
| • Nat Faxon | voiced | Unknown / Strip Club Patron | 2 Episodes |
| • Ioan Gruffudd | voiced | Gabriel Byrne | Medic / Unknown | 2 Episodes |
| • Suzanne Cryer | voiced | Babette / Unattractive Girl #1 / Misty | 2 Episodes |
| • Joe Lo Truglio | voiced | Freddy / Various | 2 Episodes |
| • Elias Koteas | voiced | Jim | 2 Episodes |
| • Zach Galifianakis | voiced | Norman | 2 Episodes |
| • Peter Lurie | voiced | Man at Bizarre | 2 Episodes |
| • Skyler Gisondo | voiced | Matty Moyer / Unknown | 2 Episodes |
| • Harve Presnell | voiced | Judge | 2 Episodes |
| • Chris Cox | voiced | George W. Bush / Unknown | 2 Episodes |
| • Kristen Schaal | voiced | Girl / Librarian | 2 Episodes |
| • Anjelica Huston | voiced | Superintendent Ellen Riggs | 2 Episodes |
| • Stark Sands | voiced | Tino | Conservative #1 / Williams | 2 Episodes |
| • Brian George (2) | voiced | Ali | Prince | Guy #3 / Ali | 2 Episodes |
| • Odile Corso | voiced | God / Angelina Jolie | 2 Episodes |
| • Lew Schneider | voiced | Mr. Billdocker / Various | 2 Episodes |
| • Terri Lyn Rodriguez | voiced | Unknown / Lindsay Coolidge | 2 Episodes |
| • J. Lee | voiced | Leprechaun / Wesley Snipes | 2 Episodes |
| • Dan Fogler | voiced | Unknown | 2 Episodes |
| • Josh Robert Thompson | voiced | Various | 2 Episodes |
| • Randy Spears | voiced | John Q | 2 Episodes |
| • Dizzy Galette | voiced | Various / Tyler | 2 Episodes |
| • June Diane Raphael | voiced | Unknown | 2 Episodes |
| • Gabourey Sidibe | voiced | Party Girl / Herself | 2 Episodes |
| • Dan Navarro | voiced | Cilantro / Various | 2 Episodes |