After supervillain Shredder escapes custody, he joins forces with mad scientist Baxter Stockman and two dimwitted henchmen, Bebop and Rocksteady, to unleash a diabolical plan to take over the world. As the Turtles prepare to take on Shredder and his new crew, they find themselves facing an even greater evil with similar intentions: the notorious Krang.

The four turtles travel back in time to the days of the legendary and deadly samurai in ancient Japan, where they train to perfect the art of becoming one. The turtles also assist a small village in an uprising.

The Turtles and the Shredder battle once again, this time for the last cannister of the ooze that created the Turtles, which Shredder wants to create an army of new mutants.