April O'Neil, ace reporter for Channel 6, investigates recent break-ins, allegedly by Ninjas. Resulting in the thefts of numerous technologies, however, a chance encounter with a gang of thieves soon leads her to a bigger story when she is saved from the criminals by four mutant ninja turtles. The Turtles take April back to their lair, and, after getting better acquainted, April learns they are good hearted mutants. They decide to investigate the thefts together and their efforts lead them into an encounter with the mysterious ninjas, The Foot Clan, and their leader, Shredder.

The Shredder kidnaps Splinter in an attempt to lure the Turtles to his own cause. In order to rescue Splinter, the Turtles must enter the Shredder's mobile fortress, The Technodrome and brave it's dangerous weaponry. Even if they can, they must still confront The Shredder himself, who is armed not only with the nature of their origin, but also with his own mutated henchmen, Bebop, and Rocksteady.

Baxter Stockman, a mad scientist, is showing an exterminator his new invention a rat catching robot called Mousers. The exterminator rejects Stockman's offer, however Shredder decides to buy his inventions. He unleashes a dozen mousers into the sewers they are easily defeated by Splinter. The Turtles track the one responsible for the mechanical rats to his hide where they encounter Krang.

Shredder experiments with the Inter-Dimensional Portal, hoping to contact Krangs' Rock Soldiers and prepare an invasion of Earth. A group of fun-loving aliens called the Neutrionos, renegades in Krang's dimension, take advantage of the Portal's opening and use it to arrive on Earth.

Shredder lures Splinter into The Technodrome, this time with the promise that a weapon in his possession can restore the sensei to human form. The Turtles confront a giant-sized Krang, now in a new body, in the heart of New York City. The five then battle the invading Dimension X troops inside The Technodrome, resulting in the banishment of the fortress, and it's insidious occupants, into Dimension X itself.