Dean, Roman and Randy Orton are avatars of the Saint of Killers, and the only people in the world that can wield his guns; magic revolvers created by the Angel of Death and will destroy anything, mortal and immortal alike. Though they humanity's sole hope against invading demons from Hell, there are other forces who will stop at nothing to control the Saint.

"This isn't a prank, Randy." Bo's earnestness was almost convincing. "John didn't put me up to anything. In fact, when I tried to talk to him, he just muttered something about me not seeing him, then ran away."

US Deputy Marshals Reigns, Rollins and Ambrose are sent out to bring in the deadly outlaws known as the Wyatt Family. They soon learn that the Wyatts are not what they seem and they will need supernatural help if they are to survive. But that help comes at a very high price for Roman who must save Dean and Seth before they are sacrificed to Sister Abigail.