Captain Underpants and the Big, Bad Battle of the Bionic Booger Boy

At demonstration speech day, George and Harold show off the "Squishy"; two ketchup packets under a toilet seat. But Melvin forces everyone to watch his demonstration, the "Combine-o-Tron 2000", which he uses his hamster Sulu and a robotic hamster body he built to show off. Melvin orders Sulu to do some tricks for the class, but the hamster's able to spank Melvin himself. After noticing the scene, George and Harold adopt Sulu, who happily joins the two. Meanwhile, Ms. Ribble uses a Squishy on an already grumpy Mr. Krupp, who believes that George and Harold are responsible. When Mr. Krupp finds them in the lunchroom, Melvin almost immediately tattles on the boys and Mr. Krupp sends them to detention, causing them to make a libelous Captain Underpants comic starring Melvin.

Having read the comic, Melvin angrily goes home and builds a super-powered robot to combine himself with using the Combine-O-Tron. However, Melvin sneezes at the last second from his allergy to cats and gets combined with the robot and boogers, turning him into the Bionic Booger Boy. Eventually, he even acquires his own drinking fountain. The cold and flu season begins, however and when the class visits a tissue factory, owner Snoddy offers free tissues, but Melvin becomes gigantic as a natural defense. George turns Mr. Krupp into Captain Underpants and the man saves his secretary, Miss Edith Anthrope. Her wet kisses turn him back and Melvin devours him, but Sulu defeats Melvin using large novelty items from warehouses.

George's suggestion, reversing the batteries in the Combine-o-Tron, surprisingly works, and only three robotic booger globs fly off. However, Mr. Krupp and Melvin's brains have accidentally switched bodies. While Melvin/Mr. Krupp boasts about the Combine-O-Tron saving the day, Mr. Krupp/Melvin tries to get the boys in jail. Suddenly, the globs come to life and smash the Combine-O-Tron.

The globs start chasing George, Harold, Sulu, Melvin and Mr Krupp. They reach a dead end, but where Sulu spits them out into outer space. After a number of incidents, George and Harold discover the body mix-up. Since it would take Melvin six months to build another machine, George suggests going back in time, which makes Melvin snap his fingers, causing Mr. Krupp to turn into Captain Underpants and fly away. George and Harold are forced to tell the secret and Melvin orders them to create a comic about him, before setting to build. The next day, Melvin is furious that the former mentioned depicts him as uncool, but soon explains to them that if the machine's used two days in a row, something will place the world in a catastrophe. He also gives them the "Forgetchamacallit 2000", against one's short-term memory. George and Harold decide two days back to get to Melvin's "Combine-O-Tron 2000.

However, the boys end up in the Cretaceous period and get a female Quetzalcoatlus, who they nickname "Crackers". The two go to when Singerbrains is driving to the police station. George convinces her she is dreaming because of "the dinosaur's presence", etc. Harold sends Crackers back, then they erase her memory, get the Combine-O-Tron and travel to the present. Meanwhile, Captain is helping two old ladies cross the street. He successfully rescues a cat from a tree at the same time, but accidentally leaves the ladies up there. They, and other victims of him, including Anthrope, form an angry mob. Melvin" finds Underpants and switches one another back.

In space, the boogers land on a spaceship, hanging on as it returns to Earth, before they start destroying the space center. Underpants goes off to help, but discovers that his powers were taken by "Big Melvin", who refuses to help unless George and Harold change the comic. Captain Underpants and the boys are cornered at a local store and starts throwing random items stacked outside. By chance, Carl is killed upon swallowing an orange. The other boogers become cautious, but Captain Underpants makes a deliberately annoying "Underpants Dance", making them climb up his chosen building, right into a well-placed orange-made Squishy.

Soon, "Big Melvin" lies to the Eyewitness News crew (including spanking Captain Underpants) while George and Harold sneak back to school, returning with the machines. Captain Underpants gets his powers back, then the crew and audience's memories are erased. The angry mob find Melvin (who no longer has superpowers) and chase him in retribution. When the boys return to their clubhouse, George finds out that Harold didn't really send Crackers back. Harold is keeping Crackers as another pet, which George decides she could stay in the present for just one night. But the next day, when George, Harold and Sulu are ready to take Crackers back where she belongs, the time machine malfunctions.

Melvin is a huge snitch who tattles on everything. One day, Melvin tells on a bank robber to the police, which makes him so famous that he wins the election he takes by a landslide. Melvin first becomes Mayor. Over the days people make him the protecter of the town. The jails fill up so quickly that he is forced to create a giant robot one. Underpants easily escapes out of the robot jail. He does not want to hurt the people inside, but pours a giant bottle of "Mrs. Plop's Prune Juice" into the robot jail's mouth, making it shoot out the prisoners. He then breaks open Melvin's glass dome. Melvin is now sent to the "jail for dumb kids." The town goes back to normal.

While driven to the toxic waste dump, a waste barrel falls on a cotton field, where the cotton grows to an unbelievable size. One day, is it made into "Glow In the Dark underwear" and Melvin's mother gives him one from a big sale. Overnight, Melvin grows into a giant. The police spots him the next morning and calls the military. Then Underpants flies in and notices a tag on the back saying it will shrink if washed. Then, Melvin takes Underpants to the lake, but his underwear becomes soaked. Underpants asks a passing bird to pop Melvin, which it does, before Melvin is whisked away to a "Jail for Dumb Stupid Nerds".