The film received positive reviews, with critics praising the animation, humor, faithfulness, references to its source material, and voice acting.

[7] In Piqua, Ohio, best friends and next-door neighbors George Beard and Harold Hutchins create comic books, their latest creation being a superhero named Captain Underpants.

They are fourth-graders at the un-fun, depressing Jerome Horwitz Elementary School, where their excessive pranks to cheer up their fellow students put them at odds with their cruel principal Benjamin Krupp.

With Captain Underpants as principal, the school becomes a livelier place (reinstating the art room and bringing in a carnival), but a rainstorm turns Captain Underpants back into Mr. Krupp (and thus leaving him unable to change back of the heavy rain), officially places George and Harold in separate classes.

Poopypants uses Melvin's brain, which lacks the part that causes laughter, to power a ray that turns the students into dull, humorless zombies.

The toxic leftovers give Captain Underpants real superpowers and, with George and Harold's help, he defeats and shrinks Poopypants, who escapes on a bee.

Unable to control Captain Underpants forever, George and Harold destroy the Hypno-Ring to permanently change him back into Mr. Krupp, but swear to remain friends.

After unwittingly snapping his fingers, Mr. Krupp is once again transformed into Captain Underpants, to Edith's surprise and admiration, and he flies away with George and Harold to face their next adventure together.

In January 2014, the cast was announced; Ed Helms as Captain Underpants / Mr. Krupp, Kevin Hart as George Beard, Thomas Middleditch as Harold Hutchins, Nick Kroll as the "insidious villain" Professor Poopypants, and Jordan Peele as George and Harold's "nerdy nemesis" Melvin Sneedly.

[17] A month later, Letterman left the project but came back as an executive producer, and David Soren, the director of Turbo, entered talks to direct the film.

In an interview with Los Angeles Times, Pilkey said: "Once I met David, it was like a huge load fell off my back; I was like, 'I don't even have to think about this anymore.

In an interview with MovieFreak, he mentioned, "We actually looked at a lot of John Hughes movies for inspiration, like Ferris Bueller's Day Off and Weird Science.

[20] The film also features music from Adam Lambert, Cold War Kids member Nathan Willett, and Lil Yachty.

[25] The film was chosen along with the 2017 Columbia Pictures and Sony Pictures Animation film, titled The Emoji Movie, to inaugurate the removal of Saudi Arabia's cinema ban through a double feature screening on January 13, 2018, organized by Cinema 70; they were the first two movies to be given an official public screening in the country in 35 years.

The site's critical consensus reads, "With a tidy plot, clean animation, and humor that fits its source material snugly, Captain Underpants: The First Epic Movie is entertainment that won't drive a wedge between family members.

Although Seitz pointed out that the film is hampered by "a rushed, jumbled quality" and has "tiresome" features that he says are common to DreamWorks, such as "frenetic action scenes ... and the use of workhorse pop songs", he emphasized that "[t]hey've approached this compendium of elemental slapstick and unabashed childishness with the reverence that the Coen brothers brought to No Country for Old Men."

He further added that the inclusion of the flipbook interludes are the film's best parts, especially in having the pages accidentally be torn similar to the real books, stating that "[i]t's not often that a movie puts a spotlight on a mundane ritual in your own life that you never realized was profound and says, 'You probably forgot about this, but I want you to remember it and savor it because it meant something.

On December 9, 2020, DreamWorks Animation announced that a feature film adaptation of Dog Man (another one of George and Harold's comic creations) was in the works by director Peter Hastings, the showrunner for The Epic Tales of Captain Underpants.