Enraged by the death of his wife and daughter caused by a massive virus outbreak in New York, Sgt. James Heller sets out to seek revenge against Alex Mercer in the Red Zone. There, he comes face to face with the infected Mercer, but is unable to hurt him. Impressed by Heller's determination, Alex infects him with the Blacklight virus and invites him to fight on his side, telling him that Blackwatch is responsible for his family's death.

Heller starts using his shapeshifting abilities and attack the mighty Blackwatch to find the people responsible. Playing as the genetically enhanced shape-shifting PROTOTYPE weapon, players will kill and consume their way to avenge Heller's family, and put an end to the Blacklight virus that has caused widespread death and destruction.