The game is set in the fictional Hope County, Montana, where a preacher named Joseph Seed has risen to prominence. Seed believes that he has been chosen to protect the people of Hope County from an "inevitable collapse" and has established a congregation called Eden's Gate. Ostensibly, this is to fulfill his mission of leading the people to salvation in reality, Seed is a radical preacher and Eden's Gate is a militaristic doomsday cult. Under his rule, Eden's Gate has used both coercion and violence to forcibly convert the residents of Hope County, and intimidation to keep them from contacting the outside world for help. When an attempt to arrest Seed ends with the deaths of several lawmen, the player is swept into the armed conflict between Eden's Gate and the remaining Hope County residents, who are organizing themselves into a resistance movement.
The player takes on the role of a sheriff's deputy who is part of the task force sent to Hope County to arrest Seed. Seed has assumed the title of "the Father" and maintains control over Hope County with the aid of his siblings, known as "the Heralds": Jacob, a former military officer that oversees their armed soldiers; John, a lawyer that has been able to acquire much of the land in Hope County for Eden's Gate; and Faith, who acts as a pacifist to bring the people to believe and trust in her older brother. The residents of Hope County opposed to Seed include Pastor Jeffries, a local church leader that has seen his congregation taken by Eden's Gate; Mary May, a bartender whose father was driven to suicide by the cult; Nick Rye, a cropduster pilot who wants to eliminate the influence of the cult in order to build a better future for his children and Grace Armstrong, a mercenary sniper who helps the player in fighting the cultists.