Act I ("Overture") The "The Cat in the Hat", acting as narrator, sits on a bare stage, save for an odd multi-colored circle background ("Oh, the Thinks You Can Think!").
In the Jungle of Nool, where Horton the Elephant is bathing ("Our Story Begins"), he hears a strange noise coming from a speck of dust. He rescues the speck and places it on a clover to guard ("Horton Hears a Who"). The other animals mock him, except for Gertrude McFuzz, who admires his compassion and begins to fall in love with him ("Biggest Blame Fool"). Horton hears the mysterious voice again, which belongs to the Mayor of "Who", a dust-speck planet covered with microscopic inhabitants called Whos. The Cat in the Hat zooms in on the dust speck as the Whos are revealed. The Mayor, his wife and the rest of the Whos reveal their planet is so small and fragile they are constantly threatened with death, and beg Horton to help protect them. His resolve strengthened, Horton promises he will guard the dust speck ("Here on Who")
The mayor's son, Jojo, is scolded by his parents for thinking "thinks", imaginary thoughts which disrupt his school classes and anger his teachers ("A Day for the Cat in the Hat"). Although he tries not to think thinks, he starts to imagine his tub is McElligot's pool where his thinks soon spiral out of control ("It's Possible") and cause time to fly. Frustrated, the Mayor and Mrs Mayor agree to "lay down the law" but are unsure of just how to discipline their son ("How to Raise a Child"). After receiving a brochure, they decide to send him to a military school run by a misguided warmonger named General Genghis Khan Schmitz, who is preparing to go to war with those who eat their bread butter-side down ("The Military").
Horton meets Jojo, with whom he bonds as a fellow social outcast ("Alone in the Universe"). The next day, Gertrude (whose feelings for Horton are still strong) laments that her tail only has one feather, believing its sorry sight is the reason Horton is not noticing her ("The One Feather Tail of Miss Gertrude McFuzz"). Mayzie LaBird, whose tail is enormous and dazzling, advises Gertrude to obtain pills from Doctor Dake, which Mayzie promises will make her tail "almost as amazing" as hers ("Amayzing Mayzie" / "Amayzing Gertrude"). Gertrude is so excited about her tail, she overdoses.
Horton is ambushed by a group of mischievous monkeys, the Wickersham Brothers ("Monkey Around") who steal the clover and give it to an eagle, Vlad Vladikoff, who drops it into a large patch of identical clovers ("Chasing the Whos"). The Cat in the Hat freezes the action and delivers an ironically cheery tune about how fortunate the audience is not to be the Whos ("How Lucky You Are"). Horton looks for the clover, while Gertrude tries to attract his attention. Horton, however, is so intently focused on his mission he does not notice her, and a dejected Gertrude retreats to take more pills ("Notice Me, Horton"). Mayzie LaBird, who has just been abandoned by her lover and left with an egg, interrupts Horton's search and begs him to sit on it so she can take an afternoon off ("How Lucky You Are" (Reprise)). Horton reluctantly agrees, and Mayzie flies away, but does not return. As winter approaches, Horton is captured by hunters. Gertrude makes an attempt to rescue him, but the size and weight of her new tail does not allow her to fly ("Horton Sits on the Egg").
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Act II ("Entr'acte") ("Our Story Resumes") Horton is transported to New York City ("Egg, Nest and Tree") and auctioned off to the circus ("The Circus McGurkus"), lamenting his sorry state ("The Circus on Tour"). Mayzie is lazing about in Palm Beach, where she admits she tires of the monotony of sunbathing ("Mayzie in Palm Beach"). She decides to attend the Circus, where she reunites with Horton and the egg. Horton pleads for her to take it back, but Mayzie refuses, and gives the egg to Horton to keep forever ("Amayzing Horton"). Alone with the egg, a sorrowful Horton vows to nurture it himself ("Alone in the Universe" (Reprise)) and sings a lullaby about a magical world called Solla Sollew.
On Christmas Day, Jojo and his fellow cadets are deployed to fight in the Butter Battle. Jojo finally confronts General Schmitz, declaring his belief in the immorality of the war and deserting the army. However, he causes an explosion which is thought to have destroyed him ("Green Eggs and Ham" ("Transition to Butter Battle")). Jojo's parents learn of his alleged death ("A Message from the Front") at the Christmas Pageant. The Cat in the Hat, however, reenacts the scene, so the audience sees that Jojo is actually alive, but lost in some dark place far from Whoville ("Lost in Whoville"). Jojo forgives the Cat in the Hat for his perceived offenses, taking his advice and trusting his hunches to lead him back home. He and his parents share a joyful embrace ("Havin' a Hunch").
At the Circus, Gertrude reappears and frees a bewildered Horton. She has swallowed her pride, got her tail feathers plucked, and flew across the world to rescue Horton the elephant and find the Whos' clover ("All for You"). Ecstatic that the Whos are finally safe, Horton begins to fall in love with Gertrude. However, their happiness is crushed as the Sour Kangaroo and the Wickersham Brothers drag Horton back to the Jungle of Nool, and put him on trial for the crimes of "talking to a speck of dust and loitering on an egg". Gertrude and Horton make a stand at the trial, but in vain; Yertle the Turtle orders the clover to be boiled in a kettle of beezlenut oil. Aghast, Horton begs the Whos to shout to prove their existence, which nearly fails until Jojo comes up with a "think": the word "Yopp!" whose peculiar sound is just enough to reach the jungle creatures' ears ("The People Versus Horton the Elephant"). The court acquits Horton and the Sour Kangaroo repents, swearing that she will help Horton protect the Whos. In Whoville, Jojo is honored as "Thinker Non-Stop" and finally wins the appreciation of his parents.
The egg hatches, and a tiny "Elephant-Bird" emerges. Horton panics, realizing he can't handle flying progeny, but Gertrude promises him that as Horton "teaches him land" she will "teach him sky". They agree to raise the child together ("Alone in the Universe" (Reprise)). The Cat in the Hat sums things up with "Oh, the Thinks You Can Think!" (Reprise) and "Green Eggs and Ham".