The book is about a human schoolgirl named Mayzie who one day suddenly sprouts a bright yellow daisy from her head. It causes alarm in her classroom, family, and town, until an agent makes her a celebrity. The Cat in the Hat is seen serving as the narrator to this story who helps Mayzie to understand her problem and persuade her to go back home. The book has a mini-song titled "Daisy-Head Mayzie" which her classmates chant.
In 1995, prior to its actual publication, the book was adapted into a special for television on TNT. The special, which was produced by Hanna-Barbera, can be found as a bonus feature on the Horton Hears a Who! Deluxe Edition DVD.
In 2011, Daisy-Head Mayzie was made a meetable character at Seuss Landing at Universal's Islands of Adventure.