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.

In 1926, Newt Scamander arrives at the Magical Congress of the United States of America with a magically expanded briefcase, which houses a number of dangerous creatures and their habitats. When the creatures escape from the briefcase, it sends the American wizarding authorities after Newt, and threatens to strain even further the state of magical and non-magical relations.