- Dave Willis
- Â Meatwad / ... 147 episodes, 2000-2023
- Dana Snyder
- Â Master Shake / ... 145 episodes, 2000-2023
- Carey Means
- Â Frylock 143 episodes, 2000-2023
- Matt Maiellaro
- Â Err / ... 48 episodes, 2001-2015
- C. Martin Croker
- Â Dr. Weird / ... 45 episodes, 2000-2012
- Schoolly D
- Â Narrator / ... 3 episodes, 2000-2013
- George Lowe
- Â Cop / ... 24 episodes, 2002-2015
- Andy Merrill
- Â Oglethorpe / ... 23 episodes, 2001-2015
- Mike Schatz
- Â Emory / ... 20 episodes, 2002-2015
- Ned Hastings
- Â Self / ... 11 episodes, 2003-2015
- Nick Ingkatanuwat
- Â Tree / ... 11 episodes, 2003-2015
- Chris Ward
- Â MC Pee Pants / ... 7 episodes, 2002-2015
- Dana Swanson
- Â Actress / ... 6 episodes, 2009-2013
- H. Jon Benjamin
- Â Mothmonsterman / ... 5 episodes, 2001-2009
- Jay Wade Edwards
- Â Assistant / ... 5 episodes, 2003-2012
- Vishal Roney
- Â Cliff / ... 5 episodes, 2002-2011
- Eugene Mirman
- Â Dr. Eugene Mirman / ... 5 episodes, 2006-2015
- Shawn Coleman
- Â Paul / ... 5 episodes, 2008-2012
- Mary Kraft
- Â Computer / ... 4 episodes, 2001-2013
- Jim Fortier
- Â Satan / ... 3 episodes, 2003-2006
- Scott Hilley
- Â Flargan / ... 4 episodes, 2001-2012
- Dan Triandiflou
- Â Creditor 4 episodes, 2011-2015
- Larry Murphy
- Â Dominic / ... 4 episodes, 2011-2015
- Don Kennedy
- Â Assisted Living Dracula / ... 3 episodes, 2001-2010
- David Cross
- Â Happy Time Harry / ... 3 episodes, 2002-2008
- Patton Oswalt
- Â DP / ... 3 episodes, 2003-2006
- Jon Glaser
- Â Oog / ... 3 episodes, 2003
- Jon Schnepp
- Â The Wisdom Cube / ... 3 episodes, 2003-2009
- Todd Barry
- Â Romulox / ... 3 episodes, 2002-2010
- Brooks Braselman
- Â Ghost / ... 3 episodes, 2003-2010
- Todd Hanson
- Â Napkin Lad / ... 3 episodes, 2002-2011
- Max Willis
- Â Hankwad / ... 3 episodes, 2008-2015
- Sadie Willis
- Â Meatwad's Daughter / ... 3 episodes, 2008-2015
- John DiMaggio
- Â Dr. Zord / ... 2 episodes, 2003-2015
- Nick Gibbons
- Â Drunk 3 episodes, 2010-2015
- Oliver Nichols
- Â Andre 2 episodes, 2004-2012
- Eddie Pepitone
- Â Dolores Brutananadilewski 3 episodes, 2011-2015
- Lavell Crawford
- Â Unbelievable Ron / ... 3 episodes, 2013-2015
- Scott Adsit
- Â Drewbacca / ... 2 episodes, 2008-2009
- T-Pain
- Â Dummy #2 / ... 2 episodes, 2008-2009
- Bill Hader
- Â Der Inflatable Hitler / ... 2 episodes, 2009-2010
- Tommy Blacha
- Â Mr. Wongburger 2 episodes, 2006-2009
- Kim Manning
- Â Donna Bryson / ... 2 episodes, 2004-2009
- Scott Fry
- Â Pawn Shop Owner 2 episodes, 2008-2009
- Gregory Alan Williams
- Â Freedom Cobra 2 episodes, 2011
- Brendon Small
- Â Rice Henchmen 2 episodes, 2006-2010
- Todd Field
- Â Ol' Drippy 2 episodes, 2002-2003
- Matt Harrigan
- Â Major Shake-replicant 2 episodes, 2002-2003
- Fred Armisen
- Â Poncho / ... 2 episodes, 2004-2008
- Brian Stack
- Â Don / ... 2 episodes, 2013-2015
- Francisco Guglioni
- Â Oglethorpe's Dad 2 episodes, 2013-2015
- Dan Fogler
- Â Hyper Toaster 8019 / ... 2 episodes, 2023
- Isaac Hayes III
- Â The Voice 1 episode, 2003
- Josh Homme
- Â Dummy #1 2 episodes, 2008-2012
- Steve Schirripa
- Â Dante / ... 1 episode, 2009-2012
- Paul F. Tompkins
- Â Angel / ... 2 episodes, 2010-2015
- Paul Rust
- Â Neelzebub / ... 2 episodes, 2010-2013
- Kyle Kinane
- Â Doctor / ... 2 episodes, 2012
- Henry Zebrowski
- Â Merlo / ... 2 episodes, 2013-2015
- Bobby Moynihan
- Â Space Chimp / ... 2 episodes, 2013
- Andy Daly
- Â Presbobot / ... 2 episodes, 2015
- Kelly Hogan
- Â The B.J. Queen 1 episode, 2008
- David Long Jr.
- Â Carl 1 episode, 2009
- Tom Clark
- Â The Mummy 1 episode, 2002
- Ken Osborn
- Â TV Announcer 1 episode, 2005
- Will Forte
- Â Alien 1 episode, 2006
- Andrew W.K.
- Â Andrew W.K. 1 episode, 2006
- Roberto Lange
- Â Moucus Man 1 episode, 2006
- Neko Case
- Â Chrysanthemum 1 episode, 2008
- Natasha Leggero
- Â Computer Technician 1 episode, 2009
- Michael Kohler
- Â Michael 1 episode, 2009
- Drake Stephens
- Â Latin Kid 1 episode, 2009
- Wendy Cross
- Â Co-worker 1 episode, 2013
- Tim Andrews
- Â Zen Lawn Ranger 9019 / ... 1 episode, 2023
- Tom Scharpling
- Â Willie Nelson 1 episode, 2003
- Hayden Ward
- Â Carl's Girlfriend 1 episode, 2003
- Carlos Tureta
- Â TV singer 1 episode, 2003
- Lala Cochran
- Â Sexy Woman 1 episode, 2005
- Mike Judge
- Â Alien 1 episode, 2006
- Tera Patrick
- Â Tera Patrick 1 episode, 2006
- Kristen Schaal
- Â Tammy Tangerine 1 episode, 2008
- John Kruk
- Â John Kruk 1 episode, 2008
- Diviya Roney
- Â House Hunting Wife 1 episode, 2008
- Matt Walsh
- Â Ray 1 episode, 2009
- Chuck D
- Â Chuck D 1 episode, 2009
- Vanessa Palacios
- Â Woman in Bathroom 1 episode, 2009
- Ollie Green
- Â Cool Guy 1 episode, 2011
- Rita McGrath
- Â Svetlana 1 episode, 2002
- Seth MacFarlane
- Â Wayne the Brain 1 episode, 2003
- Brian Posehn
- Â The Real Wisdom Cube 1 episode, 2003
- Zakk Wylde
- Â Zakk Wylde 1 episode, 2003
- Barry Mills
- Â Hustlin' Tom Turkey 1 episode, 2003
- Akhenaton Nickens
- Â Large Larva 1 episode, 2004
- Killer Mike
- Â Boost Mobile Phone 1 episode, 2005
- Sammy Hagar
- Â Sammy Hagar 1 episode, 2010
- Jim Brown
- Â Tattoo Artist 1 episode, 2011
- Jim Florentine
- Â Manager 1 episode, 2013
- James Austin Johnson
- Â Zenwa Steam Machine 3019 1 episode, 2023
- Glenn Danzig
- Â Self 1 episode, 2002
- Seth Green
- Â Seth Green 1 episode, 2003
- Todd Maiellaro
- Â Singer 1 episode, 2003
- Bob Odenkirk
- Â Bean Wizard 1 episode, 2004
- Sarah Silverman
- Â Robositter 1 episode, 2004
- Scott Thompson
- Â Dusty Gozongas 1 episode, 2004
- Billie Reaves
- Â Self 2 episodes, 2005-2012
- Bart Oates
- Â Bart Oates 1 episode, 2006
- Cindy
- Â Foxy Momma 1 episode, 2008
- Joe Satriani
- Â Joe Satriani 1 episode, 2010
- Steven Wright
- Â Danny 1 episode, 2011
- Patrick Byrne
- Â Mobster 1 episode, 2013
- Maurice LaMarche
- Â Zenwa Bean Machine 4019 / ... 1 episode, 2023
- Eric Wareheim
- Â Germ Master 1 episode, 2004
- Michael Hanks
- Â Narrator 1 episode, 2004
- Ashley Ward
- Â Sheila 1 episode, 2004
- Rachel Dratch
- Â Robot Wife 1 episode, 2008
- Penny Pearce
- Â Foxy Momma 1 episode, 2008
- Michael Anthony
- Â Michael Anthony 1 episode, 2010
- Matt Berry
- Â Allen 1 episode, 2011
- Tim Heidecker
- Â Basketball 1 episode, 2004
- Ted Nugent
- Â Self 1 episode, 2004
- Amanda Marks
- Â Donna Bryson / ... 1 episode, 2004
- Sam Harrigan
- Â Robot Child 1 episode, 2008
- Janeane Garofalo
- Â Donna 1 episode, 2004
- Lisa Willis
- Â Stacey 1 episode, 2004
- Molly Harrigan
- Â Robot Child 1 episode, 2008
- Maria Schneider
- Â Phil Cabinet's Wife 1 episode, 2004
- Carol Kolb
- Â Wall 1 episode, 2004
- Joe Garden
- Â Phil Cabinet 1 episode, 2004
- Chris Karwowski
- Â Tulip Sniper 1 episode, 2004
- Gillian Jacobs
- Â Carl's Wife 1 episode, 2010
- Tom Savini
- Â Police officer 1 episode, 2010
- Amber Nash
- Â Tabitha 1 episode, 2010
- Larry Miller
- Â Self 1 episode, 2010
- Robert Smigel
- Â One Hundred 1 episode, 2010
- Insane Clown Posse
- Â Themselves 1 episode, 2010
- Violent J
- Â Self 1 episode, 2010
- Shaggy 2 Dope
- Â Self 1 episode, 2010
- Nick Weidenfeld
- Â Television executive 1 episode, 2010
- Idris Elba
- Â Police Officer 1 episode, 2011
- Tom Hollander
- Â Chuck 1 episode, 2011
- Gregg Turkington
- Â Wi-tri 1 episode, 2011
- Duncan Trussell
- Â Wi-tri 1 episode, 2011
- Zach Hanks
- Â Lance 1 episode, 2011
- Brett Gelman
- Â Rocket Horse 1 episode, 2012
- Lisa Lampanelli
- Â Darlene 1 episode, 2012
- Carl Jones
- Â Zucotti Manicotti 1 episode, 2012
- Kurt Metzger
- Â Flavor Flav impersonator 1 episode, 2012
- Brann Dailor
- Â Uno 1 episode, 2012
- Brent Hinds
- Â Yahtzee 1 episode, 2012
- Troy Sanders
- Â Boggle 1 episode, 2012
- Dominik Kreilinger
- Â Totem Pole Member 1 episode, 2012
- Daniel Liebl
- Â Totem Pole Member 1 episode, 2012
- Mario Liebl
- Â Totem Pole Member 1 episode, 2012
- Andy Sandford
- Â Unnamed man 1 episode, 2012
- Kevin Gillespie
- Â Crimson Tightwad 1 episode, 2012
- Mario Moginger
- Â Totem Pole Member 1 episode, 2012
- Walter Newman
- Â Self 1 episode, 2012
- Brooks Holcomb
- Â Gerald 1 episode, 2012
- Dale Bunney
- Â Angry Table 1 episode, 2012
- Bobcat Goldthwait
- Â Zingo 1 episode, 2013
- Casey Wilson
- Â Freda 1 episode, 2013
- Mary Mack
- Â Zaffy 1 episode, 2013
- Matt Besser
- Â Chimp Alien 1 episode, 2013
- Curtis Gwinn
- Â Chimp Alien 1 episode, 2013
- Josh Warren
- Â Wabusabi 1 episode, 2013
- Rob Kutner
- Â Hippie 1 episode, 2013
- Paul Painter
- Â Wise and All-Knowing Bush 1 episode, 2013
- Jason Steinberg
- Â Mosquito 1 episode, 2013
- Phillip Tallman
- Â Condo Salesman 1 episode, 2013
- Señor Negotio
- Â Hippie 1 episode, 2013
- T.M. Levin
- Â Hippie 1 episode, 2013
- Thomas DeCoud
- Â Hippie 1 episode, 2013
- Kumail Nanjiani
- Â Frylock's bees 1 episode, 2015
- Justin Roiland
- Â Honest Abe Lincoln's Hot Links Mascot 1 episode, 2015
- Monica Rial
- Â Jubilee 1 episode, 2015
- Andrés du Bouchet
- Â Gypsy 1 episode, 2015
- Doug Stanhope
- Â The Hairy Bus 1 episode, 2015
- Greg Fitzsimmons
- Â Randy 1 episode, 2015
- Carl W. Adams
- Â Ghost of Paul Revere 1 episode, 2015
- Matthew Stanton
- Â Knappy 1 episode, 2015
- Brian Cox
- Â Anubis 1 episode, 2023
- Lance Henriksen
- Â Vanessa 1 episode, 2023
- Danny Trejo
- Â Dewey 1 episode, 2023
- Bashir Salahuddin
- Â Terry 1 episode, 2023
- TJ Hassan
- Â Blade / ... 1 episode, 2023
- Vincent Pastore
- Â Terry (uncredited) 3 episodes, 2008-2012
- Jonathan Lipow
- (uncredited) 1 episode, 2001