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Having had no luck with his inventions, Professor Poopypants takes a job at Jerome Horwitz Elementary School as the new science teacher in the hope that the children would be kind and sweet-hearted. This proves false, however, as the students all laugh at his name, paying no attention in class. This goes on for weeks, driving the Professor to the brink of insanity. He finally snaps when he reads a comic book written by George Beard and Harold Hutchins (the two main protagonists of the book series) further making fun of him. Using an enlarged version of his Gerbil Jogger 2000 invention, he holds the school hostage and shrinks them using his shrinking device, then makes them change their name to a silly name lest he shrink them down to nothing.
George and Harold (now Fluffy and Cheeseball) get Captain Underpants (now Buttercup Chickenfanny, but Captain Underpants doesn't change his name and says he's taking orders from no one) to steal Professor Poopypants' enlarging machine, but unfortunately he and the machine are shrunk in the process.
The two of them try to enlarge the school back to normal size, but get flicked off the school. Cheeseball makes a paper airplane that Fluffy enlarges. The plane flies into many threats, yet Captain Underpants rescues them and they end up in an abandoned alley. Fluffy tries to enlarge Captain Underpants (accidentally enlarging Cheeseball's right hand) to the size of Professor Poopypants' gerbil machine. Captain Underpants then fights and defeats Professor Poopypants. Once Professor Poopypants is defeated, everyone gets their names back. The boys use the shrinking and enlarging machines to get the school and Captain Underpants back to normal size. Then Captain Underpants gets soaked with water, turning back to Mr. Krupp.
Professor Poopypants is hauled off to jail. On the advice of George and Harold, he changes his name so no one will make fun of it anymore. Sadly, he chooses his grandfather's name (on his mother's side), Tippy Tinkletrousers, which the people at jail make fun of.
As Tippy Tinkletrousers, the professor returns at the end of the eighth book (Captain Underpants and the Preposterous Plight of the Purple-Potty People) and is a minor antagonist in the ninth book (Captain Underpants and the Terrifying Return of Tippy Tinkletrousers) and the main antagonist in the tenth book (Captain Underpants and the Revolting Revenge of the Radioactive Robo-Boxers).He is arguably the true main antagonist of the series, judging by his actions as the most evil villain and Captain Underpants's Archenemy. He is also confirmed to be the main antagonist of the 2017 movie.