This article is rated G, meaning it is appropriate for all ages.
Following the events of the first film, Horton the Elephant (Jim Carrey) is now accepted as a hero of the Jungle of Nool, with everyone, including the Sour Kangaroo (Carol Burnett) respecting him. But when a sourpuss bird named Mayzie (Elizabeth Banks) leaves for Palm Beach and insists that Horton watch the egg, he will go on the biggest adventure ever to protect both his home and himself.
- Jim Carrey as Horton, a kindhearted elephant who lives in the Jungle of Nool.
- Elizabeth Banks as Mayzie, a sourpuss bird who moves to Palm Beach and leaves Horton in charge of watching over her egg. In the end, she gets eaten alive by Leo for being so selfish.
- Asher Blinkoff as Horton Jr, a small animal, resembling a winged elephant; hatched by Horton from Mayzie's egg, and raised by Horton.
- Andy Serkis as Leo, the evil lion. In the end, he gets defeated by Horton.
- Jonathan Hyde as Jeffrey Van Straussman, a sinister hunter who lives nearby the Jungle of Nool and plans to turn it into a big city for rich people and businessman.
- Rob Riggle as Walter C. McDonald, Jeffrey's corporate assistant who is both greedy and maniacal.
- Steve Carell as Ned McDodd, the mayor of Whoville and a close friend to Horton.
- Danny Glover as Daryl Nash, a wise condor and a friend of Mayzie's who despises her selfish personality, and wants her to be a kinder bird than she seems.
- Alan Tudyk as Grant Cogswood, Jeffrey's lawyer who does not like elephants.
- Tudyk also voices Tex's father.
- Seth Rogen as Morton, a mouse and Horton's best friend.
- Dan Fogler as Mr. Chairman, the head of the Whoville Council.
- Fogler also reprises his role as Yummo, the leader of the Wickersham brothers.
- Amy Poehler as Salley O'Malley, Ned's wife.
- Isla Fisher as Dr. Mary Lou LaRue, a Who U teacher and one of Horton's friends.
- Jonah Hill as Tommy, one of Horton's students.
- Joey King as Katie, one of Horton's students.
- Josh Gad as Tex, the gazelle and Horton's new student.
- Carol Burnett as the Sour Kangaroo, the head of the Jungle of Nool and one of Horton's friends.
- Jesse McCartney as Jojo, Ned's son.
- Josh Filter as Rudy, the Sour Kangaroo's son.
- Laura Ortiz as Jessica Quilligan, one of Horton's students.
- Jaime Pressly as Mrs. Quilligan, Jessica's mother.
- Selena Gomez as Helga, one of Ned's daughters.
- Bill Farmer as Willie, Tommy's father.
- Charles Osgood as the Narrator.