1347. The bubonic plague sweeps across Europe. The knight Alistair, born the illegitimate son of a lord, is given the miraculous opportunity to be legitimized as his father's heir and attain the glory he seeks. In order to claim his birthright, Alistair is summoned before the Pope himself and tasked with a holy mission-track down and stop the plague's true source: Pestilence, the First Horseman of the Apocalypse.

To defeat this mighty foe, Alistair reluctantly joins forces with some outlandish companions, including a Celtic witch, an ineffective and insane doctor, a mysterious advisor to the Pope, and the talking decapitated head of a saint. As they trek across the plague-ridden continent in search of the Horseman, the ragtag bunch must fend off a deadly order of heretic knights as well as demons from hell-if Alistair and his comrades don't kill each other first.