 | Jim Carrey als Horton (voice) |
 | Steve Carell als Mayor (voice) |
 | Carol Burnett als Kangaroo (voice) |
 | Will Arnett als Vlad (voice) |
 | Seth Rogen als Morton (voice) |
 | Dan Fogler als Councilman / Yummo Wickersham (voice) |
 | Isla Fisher als Dr. Mary Lou Larue (voice) |
 | Jonah Hill als Tommy (voice) |
 | Amy Poehler als Sally O'Malley (voice) |
 | Jaime Pressly als Mrs. Quilligan (voice) |
 | Charles Osgood als Narrator (voice) |
 | Josh Flitter als Rudy (voice) |
 | Niecy Nash-Betts als Miss Yelp (voice) |
 | Jesse McCartney als JoJo (voice) |
 | Shelby Adamowsky als Hedy / Hooly (voice) |
 | Jack Angel als Old Time Who (voice) |
| Caitlin Rose Anderson als Helen (voice) |
| Emily Anderson als Heather (voice) |
 | Jan Rabson als Town Cryer (voice) |
 | John Cygan als Who (voice) |
 | Jess Harnell als Another Who (voice) |
 | Debi Derryberry als Who Mom (voice) |
 | Samantha Droke als Hildy / Holly (voice) |
 | Karen Disher als Who Kid (voice) |
 | Marshall Efron als Wickersham Guard 1 (voice) |
 | Bill Farmer als Willie Bear (voice) |
| Jason Fricchione als Joe (voice) |
 | Heather Goldenhersh als Who Girl (voice) |
 | Selena Gomez als Helga (voice) |
 | Jimmy Hayward als Obnoxious Who (voice) |
 | Joey King als Katie (voice) |
| Christina Martino als Heidi / Haley (voice) |
| Ellie Martino als Hanna (voice) |
 | Laraine Newman als Glummox Mom (voice) |
| Tim Nordquist als Wickersham Guard 2 (voice) |
 | Colleen O'Shaughnessey als Angela (voice) |
 | Laura Ortiz als Jessica (voice) |
 | Joe Pasquale als The Dentist (voice) |
| Connor Anderson als Who Child #1 (voice) |
 | Isabella Acres als Additional Voices (voice) |
 | Bob Bergen als Additional Voices (voice) |
| Jeff Biancalana als Additional Voices (voice) |
 | Madison Davenport als Additional Voices (voice) |
 | Teresa Ganzel als Additional Voices (voice) |
| Kathy Graves Toon als Additional Voice (voice) |
 | Sherry Lynn als Additional Voices (voice) |
 | Danny Mann als Additional Voices (voice) |
 | Mona Marshall als Additional Voices (voice) |
 | Mickie McGowan als Additional Voices (voice) |
 | Madison Pettis als Additional Voices (voice) |
 | Grace Rolek als Additional Voices (voice) |
| Jennessa Rose als Additional Voices (voice) |
 | Ariel Winter als Additional Voices (voice) |
 | Fletcher Sheridan als Jojo (singing voice) (uncredited) |
| Jimmy Hayward | Director |
| Steve Martino | Director |
| Bob Gordon | Producer |
| John Powell | Original Music Composer |
| Tim Nordquist | Editor |
| Ken Daurio | Screenplay |
| Cinco Paul | Screenplay |
| Bruce Anderson | Producer |
| Audrey Geisel | Executive Producer |
| Chris Wedge | Executive Producer |
| Chris Meledandri | Executive Producer |
| Arun Ram-Mohan | Lighting Artist |
| Jeannine Berger | Post Production Supervisor |
| Barry E. Jackson | Visual Development |
| Moroni Taylor | Storyboard Artist |
| Thomas Cardone | Art Direction |
| Randy Thom | Sound Designer |
| Nash Dunnigan | Set Designer |
| Michael Knapp | Set Designer |
| Kyle Macnaughton | Set Designer |
| Jake Parker | Set Designer |
| Guillermo Willie Real | Set Designer |
| Lizette Vega | Set Designer |
| Rhett Collier | Senior Visual Effects Supervisor |
| Jamie Kirschenbaum | Senior Visual Effects Supervisor |
| Alen Lai | Senior Visual Effects Supervisor |
| Randy Thom | Supervising Sound Editor |
| Dennis Leonard | Supervising Sound Editor |
| Thomas A. Carlson | Supervising Music Editor |
| Paul Downs | Animation |
| Dr. Seuss | Book |
| J.G. Quintel | Additional Storyboarding |
| Ricardo Curtis | Head of Story |
| Christian Kaplan | Casting |
| David Esneault | Lighting Director |
| Jeff Biancalana | Storyboard Artist |
| Cal Brunker | Storyboard Artist |
| Jony Chandra | Storyboard Artist |
| Karen Disher | Storyboard Artist |
| Eric Favela | Storyboard Artist |
| William H. Frake III | Storyboard Artist |
| Martin Fuller | Storyboard Artist |
| Tony Maki | Storyboard Artist |
| Chris Renaud | Storyboard Artist |
| Rafael Zentil | Storyboard Artist |
| Stephanie Arnett | Additional Storyboarding |
| Crystal Chesney | Additional Storyboarding |
| Jeff Siergey | Additional Storyboarding |
| Edmund Fong | Additional Storyboarding |
| Chris Gilligan | Additional Storyboarding |
| Frank Marino | Additional Storyboarding |
| Rich Moore | Additional Storyboarding |
| Wilbert Plijnaar | Additional Storyboarding |
