The Darkness is a first-person shooter based on the Top Cow comic of the same name. Jackie Estacado, a Mafia hit man in modern New York City, becomes possessed by an ancient evil on his 21st birthday. The curse has been passed down through the generations in his family to the first born, starting with his great great grandfather. Jackie is about to be taken out by the henchmen of Mafia don Paulie Franchetti when the curse grants him supernatural powers. He is able to eliminate the hit men and goes after Paulie next, as the Mafia don wants to kill his girlfriend Jenny Romano.

The game offers a mixture of classic first-person shooting with regular weapons, along with the powers of The Darkness. The latter cannot be used in well-lit environments. In dark areas, Jackie can combine both powers. Jackie can switch back and forth during gameplay, and as The Darkness, the viewpoint is placed lower, but with a broader point-of-view. Darkness powers allow Jackie to summon darklings (different types of creatures), summon dark tentacles that grow from his back to break through barriers and smash opponents, along with maw tentacles for close combat. Estacado can also create a black hole and force it to collapse on itself for wide-range damage, and summon darkness guns that fire lightning bolts.

The game takes place in a modern environment, but also in the fictional Otherworld and Hell. The Darkness manifests itself as a voice in Jackie's head and tries to gain complete control of the body. The force feeds on the dark and requires a live human body to exist.