Censors in the United States have been targeting the Captain Underpants series after the first book was released in 1997. The Office of Intellectual Freedom of the American Library Association reported that Captain Underpants is the book series with the most complaints from libraries due to offensive content in the United States in 2012 and 2013. Several parents accused the book of having language inappropriate for the book's target audience, children enrolled in elementary schools.

In 2006, Captain Underpants Halloween costumes created controversy at Long Beach High School in Long Island, New York. Three female students dressed up as Captain Underpants causing the principal, Nicholas Restivo, to enact a costume ban for all students. The three girls put on beige leotards and nude stockings under white briefs and red capes. According to Principal Restivo, "the appearance was that they were naked."

Although the first few books came out on a regular basis, the ninth book, Captain Underpants and the Terrifying Return of Tippy Tinkletrousers (advertised in a teaser at the end of the eighth book), wasn't released until 2012, after a six-year wait. During this time, Dav Pilkey was caring for his terminally ill father, who died in 2008. 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 second was Super Diaper Baby 2: The Invasion of the Potty Snatchers, released June 28, 2011. The third book, Captain Underpants and the Terrifying Return of Tippy Tinkletrousers, was released August 28, 2012. The fourth book, Captain Underpants and the Revolting Revenge of the Radioactive Robo-Boxers, was released January 16, 2013.

On October 20, 2011, it was reported that DreamWorks Animation had acquired rights to make an animated feature film based on the Captain Underpants series. On October 25, 2013, it was reported that Rob Letterman would direct the film, while Nicholas Stoller would write the script. It would have been the second film to have Letterman and Stoller working together, the first being Gulliver's Travels. 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. On June 12, 2014, the film was scheduled for release on January 13, 2017. Following DreamWorks Animation's reorganization in early 2015, the studio announced that the film will be produced outside of the studio's pipeline at a significantly lower cost. It will be instead animated at Mikros Image in Montreal, Canada, and it will look differently than most of DWA's films. A month later, Deadline reported that Letterman had left the project, and that David Soren, the Director of Turbo, was in talks to direct the film, but Letterman returned to the project and serves as an executive Producer with Dav Pilkey. The film was expected to be released on March 10, 2017, but in September 2015, DreamWorks Animation's The Boss Baby took over its date. The film was released on June 2, 2017.

The Captain Underpants books were reported by the American Library Association to be the most frequently challenged books in the year 2012. Dav Pilkey also mentioned this in his website. According to the American Library Association, Pilkey's Captain Underpants series was explicitly banned in some schools for insensitivity and being unsuited to age group, as well as encouraging children to disobey authority.

Novels 6–12 in the main series form one unbroken story, in which the ending of each of such novel except the last is a cliffhanger, and the next novel in sequence immediately picks up where the last one left off.

The main series of novels has developed a pattern of alliteration from the second book on—with the exception of the third book, whose "annoyingly long" title becomes a running joke in Future books.

In October 2015, the 12th book received controversy due to a reference to Harold being gay. Some elementary schools have banned the book for this reason.

DreamWorks Animation will also produce a television series based on the film and will be streamed to Netflix. An official release date has not been given out yet, but is scheduled for release somewhere in 2018.