A family secret is revealed when Lieutenant Kazou Saki arrives from Japan to arrest his brother Oroku Saki, who turns out to be the Turtles' greatest enemy. Shredder and Krang send the Technodrome from Dimension X to Earth, but Donatello re-programs it to crash in the Arctic.
A delivery boy accidentally falls into Krang's new unstable Mutagen and becomes able to transform into anyone he chooses. Shredder tricks him into helping him launch the Mutagen into space and mutate the world, but this "Mutagen Man" has other ideas.
Donatello has tricked out the Turtle Van, but while taking it for a test drive, it's stolen from him by a family of robbing hillbillies. Can Donatello get the Van back in time before his brothers find out?
Tired of fixing everything in the lair, Donatello decides to clone himself so he can work on his other inventions. However, Donatello's clone turns against him and joins the Rat King in an attempt to conquer the city with a rat infestation.
Bebop and Rocksteady botch another mutagen experiment, resulting in a giant ice creature who Bebop dubs "Frosty", and Shredder uses this monster to freeze New York solid, preoccupying the Turtles long enough for him to steal thermal explosives needed to melt the Technodrome free from the ice.
A mad professor named Mindbender creates a law-enforcement robot named "LEX" to clean up crime in New York, but LEX ultimately starts arresting numerous innocent people for the smallest infraction. With the other Turtles unreachable, Leonardo must discover his own innate skills to stop this rogue robot before he and Mindbender declare themselves dictators of the city.
Zach, the Turtles' young friend, is put into military camp by his parents after making numerous false reports of aliens, only to find two real aliens--Wingnut and Screwloose--brainwashing the cadets to be their army and must call in the Turtles to defeat them.
Frip the Polarisoid arrives back on Earth with his family for a visit, and must ultimately ask the Turtles for help in reclaiming his camera while helping them stop Krang's latest plan to conquer the city