While celebrating lieutenant Kinzie Kensington's birthday aboard their spaceship, the Third Street Saints pass the time with a game of Ouija using a board that once belonged to occultist Aleister Crowley. The seemingly harmless amusement takes a disastrous turn when the gang unwittingly makes contact with Satan himself, who announces that the Boss will marry his daughter Jezebel before dragging the Saints' leader down into the underworld. Refusing to abandon their friend, Johnny Gat and Kinzie volunteer to follow, descending into the depths of Hell to mount a rescue. Arriving in the infernal capital city of New Hades, the pair must navigate a lawless realm of the damned, seeking a way to reach Satan and free the Boss from an unholy marriage.