Raymond "Red" Reddington, one of the FBI's most wanted fugitives, surrenders in person at FBI Headquarters in Washington, D.C. He claims that he and the FBI have the same interests: bringing down dangerous criminals and terrorists. In the last two decades, he's made a list of criminals and terrorists that matter the most but the FBI cannot find because it does not know they exist. Reddington calls this "The Blacklist". Reddington will co-operate, but insists that he will speak only to Elizabeth Keen, a rookie FBI profiler.

A schizophrenic architect must embrace his madness in order to uncover the secrets of New York and prevent the Demiurge, an ancient Gnostic god that's imprisoned beneath the city, from escaping.