Captain Underpants and the Tyrannical Retaliation of the Turbo Toilet 2000

The kickball from the fifth novel finally hits Uranus, reviving the Turbo Toilet 2000. After he remembers what happened to his fallen allies, he plans to retaliate and builds a rocket scooter from the Robo-Plunger. In the original universe, he disrupts one of Melvin's experiments, prompting Melvin to try an shush him. Angered, a chase ensues until Melvin finds one of Mr. Krupp's clipped-off toenails and extracts it into DNA. He ends up defeating the Turbo Toilet 2000, but soon, people start interrupting his experiments over trivial things and after a year, Melvin finds Sulu's signal in the future and uses the Robo-Squid suit to take George and Harold back home, before he warns them of bad to come.

After turning Captain Underpants back at Mr. Krupp's, the boys try to nap as they haven't slept in 30 hours. Unfortunately, it turns out that while running from Tippy Tinkletrousers in book 10, they ended up missing a full school day, and are forced to do five hours of yard work. Upon finishing, George then realizes they have a test day tomorrow, prompting them to stay up all night to study. At morning, they fall asleep in their tree house, causing them to miss their tests. The next day, Mr. Krupp gleefully reveals that this was actually "Super Secret Test Day" and that the boys got all zeroes on their tests. He also reveals that makeup tests are prohibited and the final exams have been cancelled, meaning final grades have already been calculated; while George barely gets a passing grade, Harold fails, causing him to repeat the fourth grade, and separating the two boys in school, much to the glee of the teachers.

George convinces Harold to travel back with the suit to take their tests, but they now have duplicates from that point. After explaining to their past selves what happened, George opts for the two pairs to switch off every other day. As the Yesterday versions go to their houses that Sunday night, the original boys have a sleepover at their treehouse, watching movies while eating pizza and soda. The next morning at school, the original boys go to school to make copies of their latest comic, but are caught by Miss Anthrope. George tries to convince is dreaming, but Yesterday George and Harold suddenly arrive at the office, making her realize she has seen two versions of the boys. Fully convinced she is dreaming, she strips naked. The Yesterday versions warn the boys to stay from school, but the original boys pull some pranks that make all the school's teachers become similarly crazy. When Mr. Krupp sees the all teachers naked, and the two Georges and Harolds, he is speechless, and starts repeatedly saying "Buh-buh-bubba-bobba-hob-hubba-hubba-wah-wah." The police eventually come, and one of the teaches pants one the officers, causing all the teachers to be arrested for indecent exposure, reckless endangerment, and pantsing the police officer, while Mr. Krupp is sent to an insane asylum.

Two weeks having passed, the Turbo Toilet 2000 flies down to Earth, while George and Harold, disguised as Talking Toilets, convince the Turbo Toilet 200 to break down the asylum wall. Over the intercom, George snaps his fingers, turning Mr. Krupp into Captain Underpants, who fights the Turbo Toilet 2000 and wins, but the Turbo Toilet 2000's giant tears of pain fall on his head. Mr. Krupp directs the Turbo Toilet 2000 to George and Harold's treehouse, but the Turbo Toilet 2000 swallows him whole. While shaking the treehouse to get the Yesterday George and Harolds out, Crackers' eggs get cracked on the floor. The Yesterdays discover they are pterodactyl-hamsters, who smash the Turbo Toilet 2000 while rescuing the Yesterdays, after which Mr. Krupp is arrested as a dreaming loon. The four boys regroup, and begin to declare this as a happy ending. However, George points out that while the day has been saved, there were a lot of loose ends in the story (the city being destroyed, the school staff being arrested, there being four Georges and Harolds, and the pterodactyl-hamster hybrids having thought that the Georges and Harolds were their parents). The boys then realize that one final sequel, and say their titular "Oh no!" and "Here we go again!" catchphrases.