• Christopher McCulloch | voiced | Sgt. Hatred / Hunter Gathers / Commander / Pete White / St. Cloud / Action Man / Col. Gentleman / The Monarch / Henchman 24 / Watch / Tim-Tom Muppet / Councilman 2, 8, 9 / The Sovereign / Dr. Henry Killinger / General Manhowers / Additional Voice / Colonel Hunter Gathers / Sgt. Haine / Tim-Tom Moppet / Pirate Captain / Dr. Z / Additional Voices / Dr. Dugong / Brainulo / Ned / Prof. Impossible / Additional Pirates / Henchman 1 / Mr. Doe / Hunter / Kano / Lloyd Venture / Fantomas / Herr Trigger / Le Tueur / Mile High "Sky Pilot" / Mister Doe / Sgt. Collar / Det. Heat / Police Psychiatrist / Doe / Steve Summers / Scorpio / Copter 5 Guy / Sheriff / Tim-Tom / Henchman 86 / Henchman 87 / Dragoon / Intangible Fancy / Sovereign Head / Councilman 9 / Ro-Boy / Torrid / Monstroso / Dr. Schumpmaker / Sky Pilot / King Gorilla / Roy Brisby / Peter White / Zero / Storm Front / Tiger Shark / Ghost Robot / Fat Chance / Cody / Mr. Polygamy / Lyndon Bee / Pete "Thantos" White / Dr. Odinson / Curse / Cheetah-Man / Boar-Man / Venturestein / Mister Frost / Misc. OSI Soldiers / Teddy / Cop 1 / Radical Left / Cuckoo Clocker / Don Hell / Steppenwolf / The Nerve / Humungoloid / Kiki / Thug / Col. Hunter Gathers / Barnacle Badhul / Augustus St. Cloud / Announcer / Wes Warhammer / Narrator / OSI Sniper | 48 Episodes |
• Doc Hammer | voiced | Dr. Girlfriend / Henchman 21 / Ward / Kevin Moppet / Councilman 1 & 3 / Billy Quizboy / Billy (Whalen) Quizboy / Shore Leave / Sheila / Underground Quizboy 1 / Dr. Mrs. The Monarch / Dermott Fictel / Extra Pirates / Mr. Cardholder / Shore Leave "Holy Diver" / Go-Fish / Cardholder / Desmond / U.S. Steel / Dermott / Kevin / Red Mantle / Councilman 1 / Dermott Ficktel / The Outrider / Speedy / Rod Mantle / Rod Martin / Dermott Fichtel / Billy "Eros" Quizboy / Col. Gentleman / "Viceroy" / Toaster Face / Afterburner / 21 / Paul Monocle / Vendata / Sunsational / Rose / Investor 1 / Mantle / Mass. Pirate | 45 Episodes |
• Steven Rattazzi | voiced | Dr. Byron Orpheus / Dr. Byron Orpheus, Some Dolphin, Steven Rattazzi / Dr. Orpheus / Alastair Crowley / Fritz / Vincenzo / Haranguetan | 26 Episodes |
• James Urbaniak | voiced | Phantom Limb / Councilman 7 / Dr. Jonas Venture Jr. / Professor Fantomas / Oscar Wilde / Sovereign / Rusty Venture / The Rusties / Rusty's Women / Jonas Venture Jr. / Bowie Sovereign / Serpentine | 25 Episodes |
• Paul Boocock | voiced | Dr. Jonas Venture / Fighter Pilot, O.S.I. Instructor / Tigerriffic, Therapist, Prison Guard 2 / Highway Cop, Scared Straight Kid / Dr. Jonas Venture, Subway Bum, Taxi Driver, Voice of Impossible Computer / Sonny, Interpreter, Little Jorgé / Jonas Venture Sr. / Additional Voices / Dr. Jonas Venture Sr. / More Pirates / Sandow / Samuel Clemens / Psychiatrist / University President / Homeless Vet / Sonnystein / Gill-Man / Security Guard 2 | 19 Episodes |
• Lisa Hammer | voiced | Triana Orpheus / Triana Orpheus, Waitress 1, Waitress 2 / Triana Orpheus, Leslie Cohen, Lesliebots / Jeanie (Mrs. Tom) / Princess Tinglepants | 17 Episodes |
• Dana Snyder | voiced | The Alchemist / President Breyer / Dog-Man / Mister Sample | 16 Episodes |
• Mia Barron | voiced | Molotov Cocktease, Island Girl / Sally Impossible, Jonas Jr.'s Ibezan Houseguest / Sally Impossible / Molotov Cocktease, Debbie / Girl Hitler / Molotov Cocktease / Ladyhawk Johnson | 16 Episodes |
• Charles Parnell | voiced | Mister 1 / Mandelay / Jefferson Twilight | 12 Episodes |
• Brendon Small | voiced | Plastic Surgeon / Johnny Quest / Resistance 1 / Agent Hauser / Sgt. Hatred / Action Johnny / Surgeon / OSI Scientist / SPHINX Agent 1 / Dr. Vulcano / Master Yourname / Hector / Swifty | 10 Episodes |
• Kate McKinnon | voiced | Nikki Fichtel / Mrs. Fichtel / TBD / Margaret Fictel / Nikki Fictel / Thalia / Mrs. Fictel / Warriana / Dot Comm / Redusa / Alexis Warrington / Eenie-Meanie | 10 Episodes |
• Nina Hellman | voiced | Kim, Jollyrancher82 / Lt. Anna Baldavitch, Woman on Cell Phone / Tijuana Prostitute / J.J.'s ride to the Marina / Kim / Woman in Court / Prostitute / Lt. Anna Baldavitch, Cassie / Dr. Tara Quymn / Mz. Quymn / Nancy Quymn | 9 Episodes |
• Joanna P. Adler | voiced | Mrs. Manstrong / Myra Brandish / Val / Virginia "Ginnie" Dunne / Drew Quymn / Jackie / Greek Lady 1 / Greek Lady 2 / Greek Widows | 7 Episodes |
• T. Ryder Smith | voiced | Baron Werner Ünderbheit / Otto Aquarius / Baron Werner Ünderbheit, Soldier 1 / Baron Ünderbheit / Dean Harris / Investor 3 | 7 Episodes |
• Bill Hader | voiced | Professor Impossible / Phage / Alien Villain / Narrator / Headshot / Phineas Phage / Flying Squid | 7 Episodes |
• Toby Huss | voiced | Scaramantula / General Treister / Copy Cat | 6 Episodes |
• Hal Lublin | played | Wide Wale / Manolo / Security Guard 1 / Jaegermeister / Janitor / The Wandering Spider | 6 Episodes |
• John Hodgman | voiced | Dale Hale / Snoopy / Guard / Maybe Man / Cop 2 / Investor 2 | 6 Episodes |
• Larry Murphy | voiced | Diamond Backdraft / Man in Robe / Giorgos / L Ron / Monsenor / Bouncer / Wonderboy 5 / Don Hell's Bouncer / Newscaster / Fallen Archer / Zoo Worker | 6 Episodes |
• H. Jon Benjamin | voiced | The Master | 4 Episodes |
• Michael Sinterniklaas | voiced | Half-Jackel / D-19 / Dermott's Mom / OSI Soldiers / Security Guard / Ninja Waiter 2 | 4 Episodes |
• Mark Gagliardi | voiced | Stars & Gators / Tosh Tompkins / Enzo / Rocco / Black Maria / Ninja Waiter 1 / Monarch Henchman | 4 Episodes |
• Paget Brewster | voiced | Amber Gold / Vespertina / Councilman 11 / Waitress / Mommy Long-Legs | 3 Episodes |
• Paul F. Tompkins | voiced | Blue Morpho / Dr. Heinie | 3 Episodes |
• Nathan Fillion | voiced | Brown Widow | 3 Episodes |
• Stephen Colbert | voiced | Professor Impossible | 3 Episodes |
• Cristin Milioti | voiced | Sirena / Kate | 3 Episodes |
• James Adomian | voiced | Phineas Page / Lawyer / Phineas Phage / Night Dick / Prisoner 1 / The Termite / Guild Sniper | 3 Episodes |
• Kevin Conroy | voiced | Captain Sunshine | 2 Episodes |
• Richard Liebmann-Smith | voiced | U.N. Science Director / Mexican University Administrator | 2 Episodes |
• Terrence Fleming | voiced | Col. Bud Manstrong | 2 Episodes |
• Sue Gilad | voiced | Patty / Princess Tinyfeet | 2 Episodes |
• Stephen DeStefano | voiced | Dr. Paul Entmann / Dr. Entmann | 2 Episodes |