Detective John Hobbes(Denzel Washington), an every day honest lawman, appears at the execution of Edgar Reese, a serial killer he managed to capture, briefly conversing with him, wherein they shake hands and he speaks an ancient language which Hobbes takes as gibberish before hes executed. However, not long thereafter, murders begin to occur, apparently done by a copycat killer to Reese, with the killer calling Hobbes' house in the middle of the night each time, and then calling Hobbes at the police station the next day to clue him in on the new murder. The first victim is killed by who later becomes the second victim, who Hobbes recognizes when he sees him from a momentary meeting where he looked him in the eye while walking down the street one night. Before he was executed, Reese had spoken a riddle to Hobbes, which turns out to be a reference to a plaque at the station with one of the names scratched off. Researching it, he eventually discovers the name to have been Robert Milano, a police officer who committed suicide after coming under investigation for murders that, it turns out, he didn't commit. Curious about the copycat murders, Hobbes researches Reese and watches a tape of him before his death with his partner, Jonesey(John Goodman), noticing then that he appeared to be left-handed, even though he was right-handed earlier in life. The language he was speaking is identified as Syriac Aramaic, a biblical language and one of the tongues of Babel. After meeting with Milano's daughter, Gretta, Hobbes takes a trip out into the mountains to visit the family home where her father killed himself, discovering some strange books and a name written on the basement wall and painted over; Azazel. After identifying the meaning of the name in a dictionary, Hobbes goes to see Gretta again, who encourages him not to take this case.
Azazel is actually a demon. A mortal one who inhabits humans to survive and commit murder, switching to a different host each time one is killed or captured. He is able to move from host to host by touch, with Hobbes being a rare case where he can't enter someone by touch. Azazel is the real killer Hobbes was after before, having possessed Reese during his run as a serial killer. Azazel's failure against Hobbes has caused him to become obsessed with him, and from the time of Reese's execution, began to stalk the detective. One day at the police station, he possesses one of Hobbes friends and reveals himself to him by singing the song he sang while still inside Reese as he was gassed, switching bodies on the spot while doing so. Outside the station, Hobbes confronts Azazel with what he knows, surprising the demon somewhat, before being freaked out by seeing him swtich continuously from body to body while threatening him. Still processing this, he again confronts Milano, asking her how he was to fight Azazel if he was really what he seemed to be and learning the particulars of her religion, as well as that he might be one of the few capable of killing a mortal demon like Azazel. Not long thereafter, having already started to set him up for the murder of one of the earlier victims, Azazel begins threatening Hobbes' family, possessing his nephew, Sam, and assaulting his brother, who is like a child in his mind. Chasing him down the street in the body of Sam's friend, Azazel possesses a teacher and forces Hobbes to shoot him down, having set up the scene to happen in advance. Though this was indeed self-defense, after the investigation begins, Hobbes, who is already devastated at having been forced to kill an innocent man, is framed by Azazel further, who gives a false testimony that the killing was unprovoked through the body of his new host.
Along with this, Azazel possesses Art, Hobbes' brother, and writes something on his nephew, Sam's chest, before having him commit suicide. After Hobbes finds this out and learns from Jonesey that Stanton, their boss, was sending someone to pick him up for more questioning, Hobbes and Sam flee the house and later evade the police, before going to Gretta's, where he reasons out with Gretta that the one breath(500 cubits) that Azazel can survive for in spirit form, which had been established at one of their previous meetings, made him so powerful no man could resist him because he would then be fighting for his life. Leaving Sam with her and telling her to take him to a place where they would be safe and that no one knew about, even him, Hobbes left for Milano's family cabin again, knowing that Azazel would follow him. Along the way, he talked with Jonesey, whose phone was tapped, giving away some of his intentions to Stanton. Later that night, Stanton and Jonesey arrive at the cabin to arrest him. Jonesey wants to simply make Hobbes disappear, though Stanton talks him down and they force Hobbes to put down his gun. However, Jonesey suddenly shoots Stanton through the head, revealing Azazel has possessed him. Retreating into the cabin, Hobbes prevents Azazel from killing Jonesey and they fight for control of the gun, resulting in Hobbes shooting Jonesey in the chest. Conversing with the demon, Hobbes lights and smokes a poisoned cigarette, and taunts Azazel that they were all alone and now going to die together. After Azazel curses Hobbes for outsmarting him, he shoots Jonesey in the forehead reluctantly. Azazel emerges and inhabits Hobbes, and tries desperately to get to a new host body, but Hobbes' body dies of the poison before he can. However, Azazel emerges and enters the body of a cat nearby, surviving and escaping into the night to continue his murderous spree.