The series revolves around two fourth graders, George Beard and Harold Hutchins, living in Piqua, Ohio, and Captain Underpants, an aptly named superhero from one of the boys' homemade comic books, who accidentally becomes real when George and Harold hypnotize their cruel, bossy, and ill-tempered principal, Mr. Krupp.

From the third book onwards, Mr. Krupp also possesses superhuman strength, durability and flight as a result of drinking Alien "Extra-Strength Super Power Juice".

[2] DreamWorks Animation acquired the rights to the series to make an animated feature film adaptation, Captain Underpants: The First Epic Movie, which was released on June 2, 2017, to positive reviews, followed by a television series, The Epic Tales of Captain Underpants, which aired on Netflix from July 13, 2018 to December 4, 2020, also to positive reviews.

A 14th book titled Dog Man: Big Jim Believes was announced and set to release in Fall 2025.

[10] A video game based on the comics titled Dog Man: Mission Impawsible was released on December 6, 2024.

[15] The Captain Underpants series was explicitly banned in some schools for "insensitivity", offensive language, encouraging disruptive behavior, LGBTQ+ issues, violence, being unsuited to the age group, sexually explicit content, anti-family content, as well as encouraging children to disobey authority.

"[15] The American Library Association stated in a release by the National Coalition Against Censorship that "This year's #1 banned book, Captain Underpants... is the gift that keeps on giving.

Pilkey also announced that he would be donating all royalties from the book to organizations dedicated to stopping violence towards Asians and Asian-Americans.

[20] In 2009, he signed a deal with Scholastic for four new books, the first of which was The Adventures of Ook and Gluk: Kung-Fu Cavemen from the Future, released August 10, 2010.

The fourth book, Captain Underpants and the Revolting Revenge of the Radioactive Robo-Boxers, was released January 15, 2013.

On January 21, 2014, the cast was announced, with Ed Helms joining as Mr. Krupp/Captain Underpants; Kevin Hart as George Beard; Thomas Middleditch as Harold Hutchins; Nick Kroll as the insidious villain, Professor Poopypants; and Jordan Peele as Melvin, the nerdy nemesis of George and Harold.

[29][30] On December 9, 2020, it was announced that a feature film based on the Dog Man spin-off series is in development at DreamWorks Animation with Peter Hastings directing at the helm after his experience with Dav Pilkey's works from The Epic Tales of Captain Underpants.

[33] Dav Pilkey had looked to turn the books into a possible TV series, and he had imagined Chris Farley in the titular role.

[41] Jessica Roake, in an article published in Slate, argued that the books are well suited for young readers.

[47] The Captain Underpants spin-off series Dog Man received positive reviews from book critics.