The Sixth Gun takes place in the old west during the late 1880s. The story centers around a set of six pistols, each imbued with dark powers. The wielder of each pistol gains an ability unique to the weapon, and is tied to the pistol until their death. The main protagonists, Becky Montcrief and Drake Sinclair attempt to collect the Six and learn their secrets. Antagonists in the series include General Hume and his four horsemen, the Knights of Solomon, the Sword of Abraham, and the Grey Witch.