Nerdy loser Melvin falls into a barrel of toxic waste left by an alien insectoid warlord Dr. Killemoff who wants to pollute and take over the Earth. However, Melvin mutates into a hideously deformed superhuman Toxie and fights him.
Killemoff's mad scientist Dr. Bender creates a chemical that makes people old and senile. Toxie and his mutant friends must stop people from eating junk food with it in it. Meanwhile, Bender gets accidentally merged with airhead Fender.
Killemoff invites Toxie and his friends to a fake island resort called 'Club Fred' and sets a trap. Meanwhile, a humanoid mutant dog, Junkyard, is looking to join the Toxic Crusaders.
Killemoff bribes the mayor to condemn the Crusaders' bubble gum factory so he can use it to manufacture smog in a can.
Killemoff goes on TV to announce that he wants to help clean up Tromaville but it's a trick to get the citizens to help him create more smog.
Smogulan scientists have discovered a huge pool of high smogtane crude that could fuel a shuttle to Tromaville for all their residents. There's only one problem, it's located under the Crusaders home base-the toxic waste dump.
A mysterious stranger shows up and Killemoff creates a remotely activated smog inducer that he plans on getting into every house in Tromaville.
Humanoid insect Czar Zosta, Killemoff's boss, arrives with his huge, ugly, vain and always hungry daughter Princess Gerba of Smogula to Tromaville. She falls for Toxie and forces him to marry her or her father will destroy Earth.
Killemoff's new boss, General Garbage, wants to clone old ladies but Killemoff is more interested in getting rid of the General.
After driving off a bridge and landing in a boat full of snails, a race car driver gets super powers.
The Crusaders build a cab while the mayor and Killemoff plot to smash them.
The mayor wants the citizens of Tromaville to plant his special seeds to beautify the city but the seeds are really vicious vines from Killemoff.
Killemoff accidentally hires Toxie's mom as his new secretary.