Fyra sköldpaddor faller ner i kloakerna och blir vänner med Hamato Yoshi, en japansk man som förvisats till New York och tvingas bo i kloakerna. En dag ser han ett konstigt grönt sken som förvandlar de fyra sköldpaddorna till människoliknande varelser. Hamato förvandlas till en gigantisk råtta av det gröna skenet och blir nu sköldpaddornas sensei som lär dem allt om konsten att vara ninjas. Tillsammans med tv-reportern April O'Neil slåss sköldpaddorna mot den onde Shredder och hans kompanjon Krang.

Leonardo, Raphael, Michaelangelo and Donatello must save New York City from the evil crime lord Shredder and his assistant, Baxter Stockman. The Turtles must fight foot soldiers, mice, and gangs and get help from their sensei Splinter, her friend April O'Neil, and her partner Casey Jones in an action-packed new series.

When the Teenage Mutant Ninja Turtles acquire Mutastones from Crys-Mu, the spirit of light, they acquire the ability to enhance themselves into Super Turtles for a duration of three minutes. Meanwhile, the evil Shredder and his minions Bebop and Rocksteady stumble upon the Dark Mutastone, which transforms them into Devil Shredder, Supermutant Bebop and Supermutant Rocksteady, respectively. But the Turtles have one more trick up their shells: all four of them can combine into their ultimate form—Turtle Saint.