The basic plot of the show is that Lucy is now 21 and living in San Francisco and her father has tapped her to fulfill her destiny of being the Anti-Christ, whether she likes it or not.
While Lucy is living her life in San Francisco and her father living in his hell, three Priests known as the "Special Fathers" are on a mission from the Vatican to find and wipe out the Anti-Christ on Earth. Being the loving father The Devil is, he tries to stop them before they can accomplish their task.
Yet another layer is added when The Devil, through his advocate (voiced by Melissa Bardin Galsky) finds out that the Messiah may indeed be active again in the Earthly realm, this time as a DJ named Jesús.
Everything comes together when Lucy, The Anti-Christ, is sent on a date with a politician by her father to the very club DJ Jesús, the Messiah, is spinning at and the two begin to fall for each other.