A reporter named Kathy Lane comes to Theodor Geisel's home in order to do a report on the famous Dr. Seuss, where she meets a strange character. When Kathy asks to use him as a source, he reveals himself to be The Cat in the Hat. Curiosity allows her to open a magical book labeled "Open a book, open up your imagination", which pulls her into the world of Dr. Seuss. The Cat in the Hat shows Kathy a door which leads to a beach. On the beach, they read The Sneetches and Other Stories. Kathy then falls into a kitchen where she meets Mr. Hunch from Hunches in Bunches. They eat lunch and read McElligot's Pool.
Kathy then ends up in a jungle where she notices Horton the Elephant. She then reads Horton Hatches the Egg. The Cat in the Hat appears again. Soon, Kathy wanders into a room which is explained to be "The World of Advertising". The Ad Man and the Ad Woman explain to Kathy about Dr. Seuss in the advertising business. The room soon rocks and Kathy is transported to Mulberry Street where she meets Marco. She helps Marco come up with a story to tell his father when he gets home from walking from school.
The story changes as Kathy and Marco add exciting things to it. The story starts out as a horse pulling a cart. But it soon turns into a tale with an elephant, the mayor, planes with confetti, a Rajah, a band playing music and other things completely random. Soon, Marco keeps the story as a horse pulling a cart. He then leaves.
Sgt. Mulvaney then appears and brings Kathy to a revolving door that is shown to represent the way people rejected Dr. Seuss' first book for publishing. The Sergeant then goes through the door and disappears.
Kathy goes through the door and ends up in a hall with the Cat in the Hat. The Cat explains to Kathy about some of Dr. Seuss' dark political cartoons. An alarm goes off and he disappears.
Kathy soon walks into a room and meets The Voice of America. The Voice of America then shows Kathy the documentary Hitler Lives, which was made by Theodor Geisel and his wife.
A live-action version of the story Yertle the Turtle is then shown in a gospel-like song.
Kathy meets back up with the Cat in the Hat, who tells her the story about him. The story is acted out by a father reading the story to his two little girls.
After the story, Kathy ends up in the story of Green Eggs and Ham where she is chased by Sam I Am who tries to get her to taste the aforementioned dish.
After that, Kathy ends up in the mountains where The Grinch had lived. A lady reads her the story of How the Grinch Stole Christmas!.
Next, Kathy shows up at the street of the lifted Lorax where she put in a payment (15 cents, a nail, and the shell of a great, great, great grandfather snail) written on paper in a bucket after which The Once-ler hoisted up the bucket with all those things, collected them, brought down a speaker and told the story of The Lorax.
After planting a new Truffula Tree, marching music sounded, indicating a butter battle which represents The Butter Battle Book.
The finale segment of the film sees Kathy and the Cat in the Hat visit the library where they sing Oh, the Places You'll Go!, later they were transported back to Dr. Seuss' house where Kathy's adventure ended.Kathy Najimy as Kathy Lane
Matt Frewer as The Cat in the Hat
Paul Winchell as some of the Sneetches (voice, archive footage)
Christopher Lloyd as Mr. Hunch
Graham Jarvis as The Farmer
Brady Bluhm as Marco (McElligot's Pool)
Frank Welker dubbed the voices of Horton, Maysie, the elephant bird, Chief Yookeroo, Van Itch and re-dubbed Hitler Lives narrator
David Paymer as the Ad Man
Andrea Martin as the Ad Woman
J. D. Daniels as Marco (Mulberry Street)
Patrick Stewart as Sgt. Mulvaney
Billy Crystal as Radio Voice (The Voice of America)
Andraé Crouch as Yertle the Turtle
Bright Eyes as Mack
Robin Williams as The Father
Zelda Williams and Eleanor Columbus as The Daughters
Howie Mandel as Sam I Am Voice-Over
Eileen Brennan as Who-Villain
Boris Karloff as the Grinch (voice, archive footage)
June Foray as Cindy Lou Who (voice, archive footage)
Terry Lindholm as Once-ler (hands)
Bob Holt as the Once-ler, the Lorax, Sylvester McMonkey McBean, and some of The Sneetches (voice, archive footage)
Charles Durning as Grandfather Yook (voice, archive footage and redubbed lines)
Clive Revill as Van Itch (voice, archive footage)
The film features many of Dr. Seuss's stories, though they are edits of older adaptations, while some of the adaptations are newly created live-action versions. It also includes some of his political work, including excerpts of his short subject Hitler Lives.
- The Sneetches (originally from DePatie-Freleng Enterprises's special, Dr. Seuss on the Loose and was edited; 1973)
- Hunches in Bunches (live-action)
- McElligot's Pool (live-action)
- Horton Hatches the Egg (originally created by Warner Bros. in 1942 and directed by Bob Clampett; this cartoon is not only edited, but re-dubbed by Frank Welker)
- And to Think That I Saw It on Mulberry Street (originally created by George Pal in 1944; and the story is re-told by J. D. Daniels)
- Hitler Lives (short documentary by Warner Bros. in 1945; not only edited, but re-dubbed by Frank Welker)
- Yertle the Turtle (live-action)
- The Cat in the Hat (live-action)
- Green Eggs and Ham (live-action)
- How the Grinch Stole Christmas! (originally the famous Chuck Jones television special created in 1966; this cartoon is not only edited, but the story is re-told by Eileen Brennan, while Boris Karloff and June Foray remain their voices of The Grinch and Cindy Lou Who.)
- The Lorax (originally created by DePatie-Freleng Enterprises in 1972; the present day scenes of the Once-ler are re-created in live-action.)
- The Butter Battle Book (originally created by Ralph Bakshi in 1989; some of the verses that weren't in the special, or weren't said the correct way for the telling of the book, are added in this version and voiced by Charles Durning, who reprised his role as the grandfather, Frank Welker and Malachi Pearson.)
- Oh, the Places You'll Go! (live-action)