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The Darkness II takes place two years after the events of the first game. Jackie Estacado, the current wielder of The Darkness has used his powers to become the Don of the Franchetti crime family.

He has been unable to shake the thoughts of his dead girlfriend Jenny Romano and has since, with the help of estranged occultist Johnny Powell and his study into dark essence, contained his supernatural powers, and now The Darkness “wants out in the worst way”. A sudden, unprovoked attack on Jackie’s life while relaxing at a restaurant heralds the start of a full-scale mob war, which has clearly been orchestrated by some outside force.

The assassination attempt leaves Jackie on the verge of death and with no choice but to release The Darkness, sending him on a mission to discover the mystery of the attack and the motivations of The Darkness himself. This quest brings Jackie to an abandoned carnival and into a confrontation with Victor Valente, a mysterious figure who knows what The Darkness is and wants his power for himself.

Victor is the head of an ancient secret society known as The Brotherhood, formed thousands of years ago by a saint for the sole purpose of protecting the world from The Darkness. However the saint became corrupted and now The Brotherhood wants The Darkness for themselves.