Professor Utonium hopes to create the perfect little girls using a mixture of sugar, spice, and everything nice to make Townsville, a city plagued by criminals and villains, a better place. Things take a disastrous turn when his laboratory assistant, a destructive chimpanzee named Jojo, shoves the Professor, causing him to accidentally break a container of Chemical X, a mysterious substance that spills into the mixture, which explodes in Jojo's face. The Professor finds that the experiment was a success, having produced three little girls whom he names Blossom (the smart and mature one), Bubbles (the cute and bubbly one), and Buttercup (the tough and scrappy one). However, these girls also have superpowers as a result of the additional Chemical X, though they all immediately grow to love each other as a family.
On their first day of school, the girls learn about the game tag and begin to play amongst themselves, which quickly grows destructive when they begin using their powers. They take their game downtown, inadvertently causing massive damage to the city until the Professor calms them down. The Professor advises the girls not to use their powers in public for their own safety. The girls are completely oblivious to the impact they had on the town until the next day, when the citizens of Townsville begin to despise them and treat them as outcasts, and the Professor is arrested for creating the girls. When he doesn't arrive to pick them up from school, the girls are convinced he hates them as well. Despondent, the girls try to make their way home on foot, but end up hopelessly lost.
Seeking shelter from a thunderstorm in an alley, the girls are attacked by the vicious Gangrene Gang, but are rescued by Jojo, whose brain has mutated and grown as a result of the Chemical X incident, granting him great intelligence and the ability to speak with a Japanese accent. However, he was quickly overshadowed by the girls on the Professor's life and chose to leave, now living on the streets. Planning control of the city, Jojo gains the girls' sympathy by telling them that he too is a freak neglected by all. He then manipulates them into using their powers to help him build a laboratory over a volcano in the middle of town and a machine he claims will gain them the affections of the town; he also has them steal a batch of Chemical X from the Professor's lab. As a reward for their hard work, Jojo takes the girls to the local zoo and secretly implants small devices on all the primates there.
The girls return home to find the Professor being released from prison, and promise him that things will be much better. That night, Jojo teleports all the monkeys from the zoo into his volcano lair, hooking them up to his new machine and injecting them with Chemical X, turning them into evil mutant monkeys like himself. The next morning, the girls prepare to show the Professor all the "good" they did, only to discover the city being attacked by the monkeys. Jojo, renaming himself Mojo Jojo, publicly denounces the girls as willing participants of his plan, turning everyone, including the distraught Professor, against them. Crushed and dejected, the girls blast off into space.
Mojo Jojo announces his intentions to rule the planet, but his minions, now as intelligent and evil as he is, also wish to rule, and begin concocting evil plots of their own to terrorize the people of Townsville, much to Mojo Jojo's frustration. Overhearing this turmoil, and discovering that they can use their powers to combat the monkeys, the girls return to Earth, defeat the monkeys and rescue the citizens. Desperate, Mojo injects himself with vast quantities of Chemical X and grows into a giant monster, but the girls defeat him after an intense battle by pushing him off a skyscraper. Hoping to help the girls, the Professor develops an antidote for Chemical X which Mojo Jojo lands on, shrinking the defeated ape back down to size.
The girls contemplate using the Antidote X to eradicate their powers, thinking they would be accepted as normal little girls, but the citizens of Townsville protest, apologizing for misjudging the girls and thanking them for their heroic deeds. At the insistence of the Mayor, the girls agree to use their powers to defend justice in Townsville and become the city's beloved superhero crime-fighting team: the Powerpuff Girls.
|Roger L. Jackson||Mojo Jojo|
|Tom Kane||Professor Utonium|
Ka-Ching Ka-Ching the Bonobo
|Jennifer Hale||Ms. Keane|
|Jennifer Martin||Sarah Bellum|
Baboon Kaboom the Olive Baboon
Hacha Chacha the Proboscis Monkey
Woman at Zoo
|Phil LaMarr||I.P. Host|
|Rob Paulsen||Hota Wata the Japanese Macaque|
Killa Drilla the Mandrill
Blah-Blah Blah-Blah the Chimpanzee
The Doot Da D Doot Da Doo Doos
|Kevin Michael Richardson||Rocko Socko the Mountain Gorilla|
Ojo Tango the Orangutan
|Frank Welker||Various Monkeys|