The series was announced in March 2017 as a re-imagining of the Teenage Mutant Ninja Turtles franchise, initially planned for 26 episodes and a Fall 2018 launch.

Rob Paulsen, who previously voiced Raphael in the 1987 series and Donatello in the 2012 series, served as the voice director for this show rather than voicing one of the turtles directly.

WWE wrestler John Cena was cast as the voice of the villain Baron Draxum.

Each episode of the series consists of two 11-minute segments, each telling a self-contained, standalone story with hints of a larger overarching plot.

The second season was originally ordered for 26 episodes but was later reduced to 13 episodes, which aired on Nicktoons instead of the main Nickelodeon channel.

A feature film sequel, Rise of the Teenage Mutant Ninja Turtles: The Movie, was announced in February 2019 for Netflix and eventually released on August 5, 2022, introducing Casey Jones voiced by Haley Joel Osment.

To promote the series, Viacom and Nintendo held a special Splatfest tournament in the 2017 video game Splatoon 2, letting players vote on which turtle brother was best; Donnie ultimately won, beating Mikey in the first round and Raph in the finals.

IDW published a companion comic book series starting in July 2018, which included an introductory issue, a five-issue main story, a Halloween Comicfest special, and later a three-issue arc titled 'Sound Off!' in 2019.