Set in the 14th century, three women accused of witchcraft are hanged by a priest. The priest performs a ritual to prevent the bodies from coming back to life. While successfully completing the ritual for the first two of the bodies from left to right, the third takes on a demonic appearance and kills the priest. Meanwhile, Teutonic Knights Behmen of Bleibruck (Cage) and Felson (Perlman) are engaged in a (fictional) crusade, taking part in several different battles throughout the 1330s, eventually taking part in the Smyrniote crusades. After witnessing the massacre of civilians during the 1344 capture of Smyrna, the two knights choose to desert the Order and the crusade and return to Germany.
While traveling through Styria, they encounter the grotesque sight of people infected with the Black Death and soon discover that the Holy Roman Empire has been swept by the plague. Upon entering the medieval town of Marburg (the German name for Maribor once part of the Duchy of Styria, now in Slovenia), the two try to conceal their identity as deserters, but are revealed as knights by the crest on Behmen's sword, and he and Felson are arrested. They are taken to Cardinal D'Ambroise, who is infected with the plague. The Cardinal asks the knights to escort an alleged witch suspected of causing the plague, to a remote monastery where an elite group of monks reside, capable of determining if the girl is truly a witch. If she is found guilty, the monks know a sacred ritual that can cancel her powers, and stop the plague that is devastating Europe.
The two knights agree under the condition that she will be given a fair trial and that the charges of desertion against them are dropped. The Cardinal agrees, and they set out accompanied by a priest Debelzeq; Kay of Wollenbarth, a young altar boy who wants to become a knight like his deceased father; Eckhart, a knight whose family were killed by the plague; and the well-traveled swindler Hagamar who is serving as their guide to the monastery in return for a pardon. The witch, a young girl later identified as Anna, shows hatred towards Debelzeq and forms a bond with Behmen.
Shortly after setting off, the group camp for the night, and Eckhart volunteers to watch the witch for the first night. After a while, Debelzeq comes to relieve Eckhart, who decides to remain with him. He tells Debelzeq about his daughter Mila, who resembled Anna. When Eckhart gets up to leave, Anna becomes hysterical at the prospect of being left alone with the priest, attacking him and grabbing his key to the cage. She escapes and flees toward a nearby village. The search for her leads the group to a mass grave, where Eckhart has visions of his dead daughter. Running after the visions, he impales himself on Kay's sword and dies. When they recapture her, the tearful Anna explains that she only ran away for fear of Debelzeq. One man down, the group become less trusting of Anna. The group manage to successfully cross a rickety rope bridge, during which Anna saves Kay from falling to his death by grabbing him with one hand, showing an unnatural strength. The group enter the dark forest called Wormwood, where Hagamar attempts to kill Anna so the group can go home, only to be stopped by the others. Anna appears to summon wolves, who chase the group and kill Hagamar. An enraged Behmen tries to kill Anna, but is stopped by Debelzeq and Felson, who points out that the monastery is in sight.
Arriving at the monastery, the men find all of the monks have been killed by the plague but locate the Key of Solomon, an ancient book filled with holy rituals used to defeat evil. The men confront Anna, with Debelzeq beginning to perform a ritual used on witches. However, as Anna begins precisely recanting stories from Behmen's past, Debelzeq comes to the realization that she is not a witch, and begins frantically performing an exorcism. However, the demon that is possessing Anna reveals itself and melts the metal. The demon effortlessly fights off the knights, but when Debelzeq throws a vial of holy water on it, it flies away out of sight. As the men search for the demon, they come to the realization that it isn't trying to escape, but is trying to destroy the book so that nothing can stop it. When they find a room where the monks were writing copies of the book, the demon appears, destroys the copies and possesses the dead monks' bodies to use as weapons. The three men fight the possessed monks while Debelzeq continues the exorcism ritual. During the fight, the demon kills Debelzeq, then proceeds to kill Felson. Kay picks up the book and continues the ritual, while Behmen continues fighting the demon. Behmen is mortally wounded during the fight, but Kay is able to finish the ritual and the demon is obliterated, freeing Anna. Behmen asks Kay to keep Anna safe, then dies of his wounds.