Principal Krupp once again turns into the superhero Captain Underpants in order to save the world, and Jerome Horwitz Elementary School, from the evil talking toilets and the Turbo Toilet 2000.

George and Harold have really done it this time--they've created a monster! She's faster, smarter, and more evil than anything the world has seen before--she's Wedgie Woman! When Harold and George turn fourth-grade teacher Ms. Ribble into the evil Wedgie Woman, she gives the wedgie of doom to unsuspecting people who stand in her way--including principal-turned-superhero Captain Underpants.

The monstrous Turbo Toilet 2000 is determined to take revenge on George, Harold, and Captain Underpants.

"Friends and pranking partners Miles and Niles face a tough challenge when their favorite goat and nemesis, Principal Barkin, is replaced by his stern, no-nonsense father, Former Principal Barkin, who turns the school into boot camp"--

When George and Harold hypnotize their principal into thinking that he is the superhero Captain Underpants, he leads them to the lair of the nefarious Dr. Diaper, where they must defeat his evil robot henchmen.

Having changed the course of human history after unwittingly wondering what could be worse than going to prison, George and Harold are shot through time back to kindergarten, where they are subjected to bullying and a clueless school principal.

Tired of following the strict rules of their grumpy replacement principal, second-grader A.J. and his classmates try to find a way to bring back eccentric but lovable Principal Klutz, who was fired for bringing a wild turkey to the school's Thanksgiving Day assembly.

A snotty situation ensues when Melvin Sneedley, an academically-gifted student, turns into the Bionic Booger Boy and must be stopped by George, Harold, and Captain Underpants.

Only Captain Underpants can stop the three evil space aliens who have invaded Jerome Horwitz Elementary School and turned everyone into lunchroom zombie nerds.

George and Harold hypnotize their principal who, believing he is the superhero Captain Underpants, leads them to the lair of the nefarious Dr. Diaper. They must then defeat his evil robot henchmen.