Nat Faxon as Captain Underpants / Mr. Krupp / Buffalobe (voice)

Jay Gragnani as Harold Hutchins (voice)

Ramone Hamilton as George Beard / Young Mr. Cleveland (voice)

Sean Astin as Narrator / Putter Mulligan (voice)

Dayci Brookshire as Jessica / Dressy / Smartaconda (voice)

Jorge Diaz as Melvin / Stanley Peet (voice)

Todd Grimes as Benjamin Franklin (voice)

Peter Hastings as Comic Narrator / Marlin (voice)

Evan Kishiyama as Steve "Gooch" Yamaguchi (voice)

David Koechner as Mr. Meaner (voice)

Phil LaMarr as Mr. Cleveland / Viper Chai (voice)

Erica Luttrell as Erica (voice)

Patty Mattson as Miss Anthrope (voice)

Brennan Murray as Bo Hweemuth (voice)

Nolan North as Lee Dingman / Hugo Mouthingwad (voice)