Nat Faxon (42)

Captain Underpants / Mr. Krupp (voice)

Jay Gragnani (12)

Harold (voice)

Ramone Hamilton

George (voice)

Sean Astin (47)

Narrator (voice)

Peter Hastings (58)

Comic Narrator (voice)

Jorge Diaz

Melvin (voice) / Melvin / Melvinborg (voice)

Dayci Brookshire

Jessica / Dressy (voice)

Evan Kishiyama (11)

Steve 'Gooch' Yamaguchi (voice)

Steve-O (44)

Lane Junkston (voice)

Tress MacNeille (67)

Ms. Hurd / DJ Drowsy Drawers (voice) / Ms. Hurd (voice)

David Koechner (55)

Mr. Meaner (voice) / Mr. Meaner / Mr. Neamer / Brainy Blabulous (voice) / Mr. Meaner / Flabby Flabulous (voice) / Mr. Meaner / Sergeant Boxers (voice) / Dr. Will Boryew (voice)

Erica Luttrell (36)

Erica (voice) / Werica Ang (voice) / Erica / Plungerina (voice) / Grace Wain (voice)

Clancy Brown (59)

Mr. Ree (voice) / Mr. Ree / Splotch (voice)

Laraine Newman (66)

Ms. Ribble (voice) / Ms. Ribble / Dr. Mentor (voice) / Female Cop (voice) / Ms. Ribble / Malison Saurus (voice) / Ms. Ribble / Queen Zombee (voice) / Dr. Mentor / Ms. Ribble (voice)

Patty Mattson

Miss Anthrope (voice) / Miss Anthrope / Chalice Aristocrab (voice) / Miss Anthrope / Clogneta (voice)

Maggie Wheeler (56)

Lunch Lady (voice) / Ms. Yewh / TP Mummy (voice)

Eric Bauza (38)

Rap Talkwell / Mr. Gigglenose (voice) / Robius (voice) / Rap Talkwell (voice)

Maurice LaMarche (60)

Tubbadump (voice)

Kari Wahlgren (41)

Mayor Hoppy McChapper (voice)

Stephen Root (66)

Mr. Fyde / Avacadwoe / Hush Muffleman (voice)

Brennan Murray (30)

Bo Hweemuth / Claylossus (voice)

Jim Rash (46)

Señor "Jerry" Citizen (voice)

John DiMaggio (49)

Smelly Socktopus / Suds Latherman (voice)

Rob Riggle (48)

Theodore 'Ted' Murdsly (voice)

Tudi Roche

Bernice Krupp (voice)

Trevor Devall (45)

Smartsy Fartsy (voice)

Kevin Michael Richardson (53)

Diddlysaurus / The Schmoozer (voice) / Diddlysaurus / Fingers (voice) / George's Dad / Dune Buggy (voice)

Paul Rugg (57)

Vert Ladderfeller III / Altitooth / Bivouac Ladderfeller (voice)

Lewis Black (69)

Ragely J. Snarlingtooth (voice)

Mindy Sterling (65)

Melvin's Mom (voice) / Harold's Mom / Melvin's Mom (voice)