The mutant outbreak continues to spread throughout the sewers and subway tunnels while the Turtles try to contain the threat. Back at Area 51, Baxter Stockman prepares a new body for cerebral transfer despite warnings from Agent Bishop. When Stockman's body begins to show signs of rejection, he becomes delirious, which leads to a rampage against the person he believes to have caused all his problems, April O'Neil. In the end, seeing April as his mother due to his delusions, Stockman sacrifices himself by being drowned in the East River while handing her to the Turtles and Casey. This episode was initially banned from airing on US television due to content issues.

The 2003 Ninja Turtles find their 1987 originals captured and held hostage by Hun. The 2003 Turtles defeat Hun, and the Purple Dragons and rescue their classic originals and escape to the modern Turtles' Lair. Meanwhile, the Technodrome from the 1987 TV series along with Shredder, Krang, Bebop and Rocksteady are together again and fight both versions of the turtles. Meanwhile the classic Shredder, transports the Utrom Shredder back from the ice asteroid that he was sent to after the "Exodus" episode. The classic Shredder and Krang had no idea that the modern Shredder would turn against them and sets out to erase the entire Ninja Turtle Universe, starting all the way back to the 1984 Mirage Comic series to where the Ninja Turtles are as of today, including the 1987 TV series Turtles, the live-action turtles, all the comic book turtles, and the modern TV series Turtles.

During a night of showing off their extreme sports gear, the Turtles are attacked by a monster from beneath the Earth. They trace the beast to a remote island where they uncover their old foe, Dr. Baxter Stockman, who has created vicious monstrosities to unleash on the unsuspecting public. Starting March 7, 2009, a series of 13 shorts, called "chapters," ranging from 90 seconds to two minutes in length began airing on The CW4Kids during episodes of TMNT: Back to the Sewer and Chaotic: M'arrillian Invasion, as well as being streamed on the 4Kids website a week in advance of airing on television. They comprise a single story called "Mayhem from Mutant Island."[7] On March 27, 2010 the 13 shorts were re-aired edited together under just the "Mayhem from Mutant Island" title as a so called "new" episode of TMNT: Back to the Sewer.