The story follows Horton the Elephant, who discovers a tiny dust speck inhabited by the microscopic community of Whos in Whoville. Horton hears a call for help from the speck and resolves to protect it, famously declaring, "A person's a person, no matter how small". The other animals in the Jungle of Nool, particularly Jane Kangaroo, doubt the existence of the Whos and consider Horton crazy. They attempt to remove the speck, leading to a chase that ends with Horton recovering the clover and learning that Whoville was damaged when it was dropped. The story emphasizes themes of empathy, belief, and the importance of protecting the vulnerable.