In this two-part episode, the Turtles rise to the surface for the first time since being mutated, and witness the Kraang, a race of brain-like aliens with robotic bodies, capturing April O'Neil and her father, Kirby. The Turtles attempt to rescue the O'Neils while learning that the strange green ooze possessed by the Kraang could hold many secrets relating to their mutations.
When Shredder plans to create an army of mutants, the Turtles must rely on the help of the Pulverizer, who was recruited into the Foot (to be expendable) and volunteers to gather information on the inside on their behalf. When he agrees to be a test subject for a stolen supply of Kraang Mutagen, the Turtles rescue him, but not before he recklessly gets himself mutated.
Narrowly escaping from the Shredder and the Kraang, the turtles, April, and Casey take shelter at April's family farmhouse upstate to recover and figure out how to stop the Kraang. The turtles deal with not having Splinter around and the possibility of Leo not making a full recovery, and a mysterious creature stalks the group.
A new and unfamiliar mutant known as Muckman begins to gain notoriety as New York City's 'Monster Hero.'
After an accident, Donnie finds himself slowly losing his intelligence.
Donnie experiments with April's fragment of the mystical Sol Star (which she is becoming quite obsessed with, due to its mighty power drastically strengthening and further developing her psionic abilities), but accidentally supercharges it with electricity, that stirs sudden sentience and autonomy in the crystal fragment. It then uses this to bring four of the main characters from Mikey's favorite comic book to life. Mikey easily befriends the heroes Wingnut and Screwloose, and he and Casey join them in stopping crime. But when they tell the two superheroes about the fact that they're fictional characters, and show them the Soul Star, it causes Wingnut and Screwloose to transform into insane monstrous forms. Meanwhile, Donatello becomes incessantly worried that the Sol Star fragment is affecting April's mental stability.
In an alternate, apocalyptic future that takes place fifty years later, all humans and most of the mutant population have been wiped out, due to an extremely powerful mutant explosion that had mysteriously occurred through unknown means. Only a weathered Raphael, who has most of his childhood memories lost to him, and Donatello (whose consciousness has been transferred into Metalhead) have been traveling throughout the Impossible Wasteland trying to save alive while being pursued by the Verminator and his bikers. Befriending a female meerkat warrior named Mira, the last of her tribe, who harbors the secret to "Paradise" and that she must find a wise turtle called "the Holy Chalupa."