In 1955, Harry Angel, a New York City private investigator, is contracted by a man named Louis Cyphre to track down John Liebling, a crooner known professionally as Johnny Favorite who suffered severe neurological trauma resulting from injuries he received in World War II. Favorite’s incapacity disrupted a contract with Cyphre regarding unspecified collateral, and Cyphre believes that a private upstate hospital where Favorite was receiving radical psychiatric treatment for shell shock has falsified records. Angel goes to the hospital and discovers that the records showing Favorite’s transfer were indeed falsified by a physician named Albert Fowler. After Angel breaks into his home, Fowler admits that years ago he was bribed by a man and woman so that the two could abscond with the disfigured Favorite. Believing that Fowler is still withholding information, Angel locks him in his bedroom, forcing him to suffer withdrawal from a morphine addiction. The next morning, he finds that the doctor has apparently committed suicide.
Angel tries to break his contract with Cyphre but agrees to continue the search when Cyphre offers him a large sum of money. He soon discovers that Favorite had a wealthy fiancée named Margaret Krusemark but had also begun a secret love affair with a woman named Evangeline Proudfoot. Angel travels to New Orleans and meets with Margaret, who divulges little information, telling him that Favorite is dead, or at least dead to her. Angel then discovers that Evangeline died several years previously, but is survived by her 17-year-old daughter, Epiphany Proudfoot, who was conceived during her mother’s love affair with Favorite. When Epiphany is reluctant to speak, Angel tracks down Toots Sweet, a blues guitarist and former Favorite bandmate. After Angel uses force to try to extract details of Favorite’s last known whereabouts, Toots refers him back to Margaret. The following morning, police detectives inform Angel that Toots has been murdered. Angel returns to Margaret’s home, where he finds her murdered, her heart removed with a ceremonial knife. He is later attacked by enforcers of Ethan Krusemark—a powerful Louisiana patriarch and Margaret’s father—who tell him to leave town.
Angel returns to his hotel and finds Epiphany on his doorstep. He invites her into his room, where they have aggressive sex during which Angel has visions of blood dripping from the ceiling and splashing around the room. He later confronts Krusemark in a gumbo hut, where the latter reveals that he and Margaret were the ones who took Favorite from the hospital. He also explains that Favorite was actually a powerful magician who sold his soul to Satan in exchange for stardom. He got his stardom but then sought to renege on the bargain. To do so, Favorite kidnapped a young soldier from Times Square and performed a Satanic ritual on the boy, murdering him and eating his still-beating heart in order to steal his soul. Favorite planned to assume the identity of the murdered soldier but was drafted and then injured overseas. Suffering severe facial trauma and amnesia, Favorite was sent to the hospital for treatment. After Krusemark and his daughter took him from the hospital, they left him at Times Square on New Year’s eve 1943 (the date on the falsified hospital records). Upon hearing Krusemark’s story, Angel runs into the bathroom and vomits. He returns to find Krusemark drowned in a cauldron of boiling gumbo.
Angel goes to Margaret’s home, where he finds a vase containing the soldier’s dog tag—stamped with the name of Harold Angel. Angel cries out as he realizes that he and Johnny Favorite are, in fact, the same person. Cyphre then appears, and Angel deduces that “Louis Cyphre” is a homophone for Lucifer. Cyphre reveals his identity and proclaims that he can at long last claim what is his: Favorite’s immortal soul. Angel insists that he knows who he is and has never killed anyone, but as he looks at his reflection in a mirror, his repressed memories showing him killing Fowler, Toots, the Krusemarks, and Epiphany come flooding back.
A frantic Angel returns to his hotel room, where the police have found Epiphany brutally raped and murdered. Angel’s dog tags are on her body. A police officer enters the room carrying Epiphany’s young son, who Angel realizes is his grandchild. The police detective tells Angel that he will “burn” for what he has done to Epiphany, to which Angel replies, “I know. In Hell.” Angel sees the child’s eyes glow, just as Cyphre’s had at their last meeting. During the end credits, Angel is seen standing inside an iron Otis elevator that is interminably descending, presumably to Hell. As the screen fades to black, Cyphre can be heard whispering, “Harry” and “Johnny”, claiming his dominion over both their souls.