Debi Derryberry as James 'Jimmy' Isaac Neutron (voice)

Megan Cavanagh as Judy Neutron / VOX (voice)

Mark DeCarlo as Hugh Neutron / Pilot / Arena Guard (voice)

Jeffrey Garcia as Sheen Estevez (voice)

Patrick Stewart as King Goobot V (voice)

Martin Short as Ooblar (voice)

Frank Welker as Goddard / Poultra (voice)

Rob Paulsen as Carl Wheezer / Mr. and Mrs. Wheezer / Kid in Classroom (voice)

Carolyn Lawrence as Cindy Vortex (voice)

Crystal Scales as Libby Folfax (voice)

Candi Milo as Nick Dean / Britney / PJ (voice)

David L. Lander as Yokian Guard / Gus (voice)

Carlos Alazraqui as Mr. Estevez (voice)

Jim Cummings as Ultra Lord / Mission Control / General Bob (voice)

Keith Alcorn as Bobby / Kid / Control Yokian (voice)

Kimberly Brooks as Zachary / Reporter / Angie / Libby's Mom (voice)

Andrea Martin as Ms. Winfred Fowl (voice)

Billy West as Bobby's Twin Brother (voice) / Butch (voice) / Jailbreak Cop (voice) / Old Man Johnson (voice) / Robobarber (voice) / Flurp Announcer (voice) / Yokian Officer (voice) / Anchor Boy (voice) / Guard (voice)

Mary Hart as Yokian Newscaster #2 (voice)

Bob Goen as Yokian Newscaster #1 (voice)

Dee Bradley Baker as Norad Officer (voice)

Laraine Newman as Hostess (voice)

John A. Davis as Octapuke Kid / Guard / Bennie (voice)

Paul Greenberg as Guard (voice)

Mark Menza as Yokian Incubator Operator (voice)

Jeannie Elias as Little Girl / Camera Person (voice)

Michael Hagiwara as Chris (voice)

Richard Allen as Digital Voice (voice)

Brian Capshaw as Screamer (voice)

Cheryl Ray as Screamer (voice)

Matthew Russell as Hyperactive Kid / Arena Yokian (voice)