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.

When Professor Poopypants becomes their new science teacher, George and Harold almost cause the entire planet to be taken over by a maniacal, mad-scientist guy in a giant robot suit.

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.

Harold and George's time-traveling Purple Potty lands them in an alternate universe where everything seems delightful, but evil lurks just beneath the surface, and leads to a battle between Captain Underpants and his own evil twin.

"George and Harold have been turned into evil zombie nerds doomed to roam a devastated, postapocalyptic planet for all eternity! Unfortunately, the boys can't count on Captain Underpants for help because Tippy Tinkletrousers and his time-traveling hijinks prevented George and Harold from creating him in the first place! With Tippy having changed the course of human history forever, George and Harold will have to figure out a way to change it back!"--Back...

George and Harold and their doubles, Yesterday George and Yesterday Harold, have been taking turns going to school, but when the doubles fall prey to their gym teacher, Mr. Meaner, and his method of mind control that turns students into attentive, obedient, perfect children, it is up to original George and Harold to strike back.