In 1932 an American teenage girl was apprehended in Europe after carving a path of destruction trying to track down and kill her biological father. The girl's name was Rayne and she claimed the people she killed, and her father who was still at large, were vampires. Before more information was attained, the girl disappeared. That girl is a dhampir; a product of her human mother's rape by her vampire father. Born with powers of a vampire without all of the weaknesses. She was taken in by an underground organization calling themselves the Brimstone Society - a top-secret fraternity that hunts down and destroys supernatural threats.

Agent BloodRayne, as she is now known, protects humanity from things that ordinary people shouldn't have to deal with. In the years between the World Wars, Agent BloodRayne works as a killing machine for The Brimstone Society. Two missions, five years apart, turn out to be connected by one man. For years, this man has been searching the world for powerful occult relics to bring Germany into a new age of domination. Agent BloodRayne must face this man's elite Nazi army to prevent them from releasing creatures of unfathomable terror onto the world in their unwavering quest for the artifacts.