 Jim CarreyHorton (voice) | Horton (voice) |
 Steve CarellMayor (voice) | Mayor (voice) |
 Carol BurnettKangaroo (voice) | Kangaroo (voice) |
 Will ArnettVlad (voice) | Vlad (voice) |
 Seth RogenMorton (voice) | Morton (voice) |
 Dan FoglerCouncilman / Yummo Wickersham (voice) | Councilman / Yummo Wickersham (voice) |
 Isla FisherDr. Mary Lou Larue (voice) | Dr. Mary Lou Larue (voice) |
 Jonah HillTommy (voice) | Tommy (voice) |
 Amy PoehlerSally O'Malley (voice) | Sally O'Malley (voice) |
 Jaime PresslyMrs. Quilligan (voice) | Mrs. Quilligan (voice) |
 Charles OsgoodNarrator (voice) | Narrator (voice) |
 Josh FlitterRudy (voice) | Rudy (voice) |
 Niecy NashMiss Yelp (voice) | Miss Yelp (voice) |
 Jesse McCartneyJoJo (voice) | JoJo (voice) |
| SShelby AdamowskyHedy / Hooly (voice) | Hedy / Hooly (voice) |
 Jack AngelOld Time Who (voice) | Old Time Who (voice) |
| CCaitlin Rose AndersonHelen (voice) | Helen (voice) |
| EEmily AndersonHeather (voice) | Heather (voice) |
 Jan RabsonTown Cryer (voice) | Town Cryer (voice) |
 John CyganWho (voice) | Who (voice) |
 Jess HarnellAnother Who (voice) | Another Who (voice) |
 Debi DerryberryWho Mom (voice) | Who Mom (voice) |
 Samantha DrokeHildy / Holly (voice) | Hildy / Holly (voice) |
 Karen DisherWho Kid (voice) | Who Kid (voice) |
 Marshall EfronWickersham Guard 1 (voice) | Wickersham Guard 1 (voice) |
 Bill FarmerWillie Bear (voice) | Willie Bear (voice) |
 Jason FricchioneJoe (voice) | Joe (voice) |
 Heather GoldenhershWho Girl (voice) | Who Girl (voice) |
 Selena GomezHelga (voice) | Helga (voice) |
 Jimmy HaywardObnoxious Who (voice) | Obnoxious Who (voice) |
