As a child stumbles upon a lone red-and-white-striped hat, its curious owners, the Cats in the Hats (Cat 1, 2, and 3) appear and introduce the boy to the wondrous world of Seuss (“Oh, The Thinks You Can Think!”). The Cats begin their tales with the story of Horton the elephant who lives in the Jungle of Nool with Jungle Citizens (1, 2, 3, 4 and 5) and several other unique creatures. One day, Horton is enjoying his bath when he hears a voice on a speck of dust asking for help (“Horton Hears A Who”).  Though puzzled, Horton delicately places the speck onto a clover just as Sour Kangaroo and Young Kangaroo bounce along. They inform Horton that there couldn't possibly be a person on that speck ("Biggest Blame Fool"). The Wickersham Brothers join in teasing. A Talk Show Host interviews two neighbor birds named Gertrude McFuzz and Mayzie LaBird about Horton hearing things that don’t exist. 

The cries of help return, and this time Mr. Mayor and Mrs. Mayor reveal themselves to Horton as citizens of a tiny place called Whoville, along with the rest of the Whos (“Here On Who”). At this point, the boy from the beginning becomes JoJo, their son, and is blamed for what are actually the Cats’ mischievous ways. JoJo is left to take his bath, but the Cats aren’t done leading the boy into greater adventures (“Oh, The Things You Can Think! – Reprise”). The Cats and JoJo are swept underwater with Fish all around in McElligot’s Pool (“It’s Possible – Part 1 and Part 2”). Meanwhile, Horton still guards the clover and believes in the Whos despite the other animals’ judgments (“Alone In The Universe”). 

Horton and JoJo bond in their imaginations, and just as JoJo begins to fall asleep, the Cats wake JoJo from his dream to tell him more stories, including ("The One Feather Tail Of Gertrude McFuzz"). Gertrude wanted a more extravagant appearance, ("Amayzing Mayzie"). Gertrude tries everything to impress Horton, self-conscious of her small, plain tail. The Wickersham Brothers return to steal the clover away (“Monkey Around/Chasing The Whos”). Horton chases them through great stretches of jungles, beaches and sand, but the monkeys hand over the clover to Vlad Vladikoff, a black-bottomed eagle who drops the Whos into a field of clovers. Mayzie reappears and asks Horton if he would consider sitting on her egg. Horton agrees (“Horton Sits On The Egg/Dilemma”) and finally, after fifty-one weeks, Mayzie returns. Horton pleads with Mayzie to take her egg back, but Mayzie relinquishes her responsibility. Horton tells the egg that he’ll protect it and sings the egg a lullaby (“Solla Sollew”). Just as things seem hopeless, Gertrude McFuzz appears with the clover and the Whos intact (“The Whos Return”). As Horton is reunited with the Whos, everyone returns to take Horton to court for “talking with a speck, disturbing the peace, and loitering... on an egg.” Judge Yertle remands Horton to the Nool Asylum and decides that the dust speck be boiled in a kettle of beezlenut oil. JoJo saves the day (Yopp!), and the Whos are saved! JoJo is honored as “Thinker Nonstop,” and the egg hatches into an Elephant Bird. As the adventure comes to an end (“Oh, The Thinks You Can Think – Finale”), JoJo reappears with the Cats’ hat and pulls it over his eyes, ending this story with one last reprise (“Green Eggs And Ham – Bows)”.