In the seemingly quiet town of Piqua, Ohio, a spirited duo of fourth-grade pals, George Beard and Harold Hutchins, are busy creating their signature brand of mischief. Their domain is Jerome Horwitz Elementary School, where they unleash an array of pranks that continually put them at odds with their ruthless principal, Mr. Krupp. Unbeknownst to them, their antics take a wild turn when they are caught on camera tampering with Melvin Sneedly's revolutionary invention, the Turbo Toilet 2000, a device set to change the landscape of bathroom hygiene forever.
With the intent of ending George and Harold's friendship once and for all, Mr. Krupp devises a scheme to separate them by placing them in different classes. However, George and Harold are not about to let that happen. Armed with a hypnotic device they found in a cereal box, they command Mr. Krupp to become Captain Underpants, a superhero of their own making. Transforming into this unlikely hero, he causes mayhem around town, prompting George and Harold to learn that they can revert him back to his true self by splashing him with water or a simple snap of their fingers.
To keep Mr. Krupp from lifting the spell and dividing them, the boys convince Captain Underpants that he is his secret identity. This cape-clad character soon catches the eye of Edith, the shy lunch lady, who is charmed by the principal's newfound superhero persona. Meanwhile, a sinister twist unfolds as Professor Pee-Pee Diarrheastein Poopypants, Esq. is brought in as the new science teacher, a man riddled with an irrational loathing for laughter. George and Harold quickly recognize his volatility and suspect he harbors dark intentions.
As Captain Underpants steps up as principal, the school transforms into a vibrant haven of excitement. However, a sudden downpour breaks the enchantment, restoring Mr. Krupp to his grumpy form and separating the boys into different classes. Fueled by his anger towards humor, Poopypants enlists Melvin to help him seek revenge on the school. He unleashes a colossal version of the Turbo Toilet 2000, powered by Edith's leftovers, that turns the students into mindless, humorless drones. Though Captain Underpants attempts to save the day, he is quickly overwhelmed by the noxious waste.
Caught in a tight spot, George and Harold's camaraderie proves to be their greatest strength as it disrupts the Turbo Toilet 2000, freeing their classmates from its grasp. In the ensuing chaos, Melvin finds himself ensnared in a massive roll of toilet paper, while Poopypants escapes on a bee. Thanks to the toxic waste, Captain Underpants gains real superpowers and, with the help of George and Harold, manages to defeat his adversary, restoring order at their school.
With George and Harold, known for creating the popular Captain Underpants comics, finally breaking free from the constraints of their creativity, they also liberate Mr. Krupp from his hypnosis, returning him to his normal self, a somewhat gruff yet ultimately kind educator. The boys, however, can't resist the opportunity to enhance Mr. Krupp's social life, orchestrating a delightful match between him and Edith, who proves to be an unexpectedly kind-hearted companion. This union brings about a substantial change in Mr. Krupp, transforming him from a curmudgeonly figure to a genuinely warm-hearted individual. As a gesture of his newfound appreciation for friendship, he returns the confiscated comics to George and Harold.
Just when it seems serenity has returned, chaos erupts as the toxic waste from the Turbo Toilet 2000's disastrous malfunction triggers an army of chattering porcelain toilets from a nearby scrapyard. These mischievous loos converge on the restaurant where Mr. Krupp and Edith are enjoying a romantic dinner, putting them in an alarming predicament.
In an incredible turn of events, Mr. Krupp's fingers involuntarily snap, reawakening his Captain Underpants persona to the astonishment and delight of Edith. With George and Harold joining the fray, he leaps into the sky, poised for their next exhilarating escapade together.
