Nat Faxon

Captain Underpants / Mr. Krupp (voice)

Jay Gragnani

Harold (voice)

Ramone Hamilton

George (voice)

Sean Astin

Narrator (voice)

Peter Hastings

Comic Narrator (voice)

Jorge Diaz

Melvin / Melvinborg (voice)

Dayci Brookshire

Jessica / Dressy (voice)

Evan Kishiyama

Steve 'Gooch' Yamaguchi (voice)

Steve-O

Lane Junkston (voice)

Tress MacNeille

Ms. Hurd (voice)

Erica Luttrell

Erica (voice)

David Koechner

Mr. Meaner / Mr. Neamer / Brainy Blabulous (voice)

Laraine Newman

Ms. Ribble / Malison Saurus (voice)

Clancy Brown

Mr. Ree / Splotch (voice)

Patty Mattson

Miss Anthrope (voice)

Maggie Wheeler

Lunch Lady (voice)

Maurice LaMarche

Tubbadump (voice)

Kari Wahlgren

Mayor Hoppy McChapper (voice)

Stephen Root

Mr. Fyde / Avacadwoe / Hush Muffleman (voice)

Brennan Murray

Bo Hweemuth / Claylossus (voice)

Eric Bauza

Robius (voice)

Jim Rash

Señor "Jerry" Citizen (voice)

John DiMaggio

Smelly Socktopus / Suds Latherman (voice)

Rob Riggle

Theodore 'Ted' Murdsly (voice)

Tudi Roche

Bernice Krupp (voice)

Trevor Devall

Smartsy Fartsy (voice)

Paul Rugg

Vert Ladderfeller III / Altitooth / Bivouac Ladderfeller (voice)

Kevin Michael Richardson

Diddlysaurus / Fingers (voice)

Lewis Black

Ragely J. Snarlingtooth (voice)

Fred Tatasciore

Keithicus / Rippedicus / Guardicus (voice)

Mindy Sterling

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

Thomas F. Wilson

Major Messy / Camoflush (voice)

Dawn Wells

Gumbalina Toothington (voice)

Max Koch

Laserlightmare (voice)

Toby Huss

Caesar / Cruelius Sneezer (voice)

Nolan North

Cash Networth / Salamangler (voice)