Disillusioned by the horrors of the Crusades, knights Behmen (Nicolas Cage) and Felson (Ron Perlman) decide to desert. Travelling through the plague-ravaged countryside of Styria, the two men arrive at the town of Marburg, where they are captured for their crime and taken before the formidable Cardinal D'Ambroise (Christopher Lee).
Infected with plague himself, D'Ambroise orders the men to escort a young woman accused of being a witch to a distant monastery where the monks can determine whether or not she is guilty. Accompanied by a ragtag group, including shifty guide Hagamar (Stephen Graham) and priest Debelzaq (Stephen Campbell Moore), the knights begin the journey with the accused, Anna (Claire Foy), in tow. Seemingly a normal girl, it's not long before Anna displays terrifying powers and the lives of the group are put in mortal danger as they come face-to-face with the forces of evil.