Four turtles fall into the sewers and are befriended by Hamato Yoshi a Japanese man sent to New York who was forced to live in the sewers. One day he sees a strange green glow which transforms the four turtles into human-like creatures. Hamato (now Master Splinter) changes into a giant rat from the green glow and teaches the turtles the skills of the ninja as they team up with news reporter April O'Neil to battle against Yoshi's arch enemy Shredder and Krang, an alien warlord from Dimension X.
While the Turtles work on using fragments of the Vortex Crystal to stabilize their mutations, Lord Dregg plans to use the fragments to create another Vortex Crystal to power his Vortex Transporter.
While Raphael, Michaelangelo, Donatello and Carter work on restoring Leonardo to his regular self, Mung steals all the plutonium from a power plant in order for Dregg to build a Plutonium Ray to turn Leonardo into a radioactive killer.
Mungg informs Dregg that he came across two individuals who claimed they were old acquaintances of the turtles: Shredder and Krang!
The Turtles', Shredder's and Krang's battles skills, powers, and memories are absorbed into Dregg.
Dregg and his crew plan an invasion Earth to make it his new home base, but first he has to get his transporter chip back from Shredder.
Dr. Alvin Huxley has demonstrated his breakthrough invention: a computer that thinks as fast as a human mind. The Globfather is on Earth and wants to get the protein computer for someone who is willing to pay a lot for it.
With the city breaking apart, the Turtles head to the street to investigate and see the Dreggnaut appear in the sky. With Mung's help, Dregg reprograms the transporter to open a warp in space.
Lord Dregg launches a final attack on the Ninja Turtles.