 Nat FaxonCaptain Underpants / Mr. Krupp / Buffalobe (voice) | Captain Underpants / Mr. Krupp / Buffalobe (voice) |
 Jay GragnaniHarold Hutchins (voice) | Harold Hutchins (voice) |
 Ramone HamiltonGeorge Beard / Young Mr. Cleveland (voice) | George Beard / Young Mr. Cleveland (voice) |
 Sean AstinNarrator / Putter Mulligan (voice) | Narrator / Putter Mulligan (voice) |
 Dayci BrookshireJessica / Dressy / Smartaconda (voice) | Jessica / Dressy / Smartaconda (voice) |
 Jorge DiazMelvin / Stanley Peet (voice) | Melvin / Stanley Peet (voice) |
| TTodd GrimesBenjamin Franklin (voice) | Benjamin Franklin (voice) |
 Peter HastingsComic Narrator / Marlin (voice) | Comic Narrator / Marlin (voice) |
 Evan KishiyamaSteve 'Gooch' Yamaguchi (voice) | Steve 'Gooch' Yamaguchi (voice) |
 David KoechnerMr. Meaner (voice) | Mr. Meaner (voice) |
 Phil LaMarrMr. Cleveland / Viper Chai (voice) | Mr. Cleveland / Viper Chai (voice) |
 Erica LuttrellErica (voice) | Erica (voice) |
 Patty MattsonMiss Anthrope (voice) | Miss Anthrope (voice) |
 Brennan MurrayBo Hweemuth (voice) | Bo Hweemuth (voice) |
 Nolan NorthLee Dingman / Hugo Mouthingwad (voice) | Lee Dingman / Hugo Mouthingwad (voice) |
