After years of being sheltered from the human world, the Turtle brothers set out to win the hearts of New Yorkers and be accepted as normal teenagers through heroic acts. Their new friend April O'Neil helps them take on a mysterious crime syndicate, but they soon get in over their heads when an army of mutants is unleashed upon them.

Fulfilling a promise to his deceased father, one-time outlaw Jesse Custer returns home to West Texas to take over his dad's church. Jesse's mission, however, becomes twisted when his body is overcome by a cryptic force that unleashes within him a highly unconventional power. Together with hell-raising ex-girlfriend Tulip and Irish vagabond Cassidy, the preacher-in-training embarks on a journey to find God in a world inhabited by holy, hellish, and everything-in-between characters.

Josh Futturman, a janitor by day/world-ranked gamer by night, is tasked with preventing the extinction of humanity after mysterious visitors from the future proclaim him the key to defeating the imminent super-race invasion.