Robert Thorn (Liev Schreiber), an American diplomat stationed in Italy, is told that his son died during birth. Unknown to his unconscious wife, Katherine (Julia Stiles), Robert adopts an orphaned newborn at the suggestion of the hospital's Catholic priest, Father Spiletto (Giovanni Lombardo Radice). Naming him Damien (Seamus Davey-Fitzpatrick), Robert and Katherine raise the boy. Robert's career ascends over the course of the next five years. He is named Deputy Ambassador to the Court of St. James in the United Kingdom. Following the death of the previous ambassador, Robert assumes his position and settles in a large estate just outside London. However, disturbing events begin to occur, including the suicide of Damien's nanny at his birthday party.
Robert is approached by Father Brennan (Pete Postlethwaite), who claims to have been involved with events surrounding Damien's birth. Meanwhile, photographer Keith Jennings (David Thewlis) finds that several of his photographs contain mysterious omens, including premonitions of people's deaths. A new nanny, Mrs. Baylock (Mia Farrow), is hired. Tension rises when Mrs. Baylock starts to make decisions without the consent of the Thorns, including adopting a Rottweiler for Damien's protection.
Following an incident near a chapel in which Damien attacks Katherine, she begins experiencing vivid dreams about her son, one of these involving a red-hooded jackal skeleton. When the Thorns visit a zoo, the animals react violently at the sight of Damien. Katherine begins to wonder if there is something wrong with Damien. Father Brennan confronts Robert, telling him that Damien's mother was a jackal, and that the boy is the Antichrist. He explains that Damien must die and a man called Bugenhagen (Michael Gambon), located in Megiddo, can assist. After being rebuked, Father Brennan is killed during a lightning storm.
Katherine discovers she is pregnant and is determined to get an abortion, in fear of having a child similar to Damien. Soon afterward, Damien causes an accident in which Katherine is severely injured, resulting in her miscarriage. While recovering in the hospital, Katherine confides in Robert her suspicions that Damien is evil. Robert decides to rendezvous with Jennings and search for Damien's biological mother. The pair discovers the hospital where Damien was delivered has since been demolished after a fire. They travel to Subiaco and meet Father Spiletto, who directs them to a graveyard. There they find the grave of Damien's mother, who is revealed to indeed have been a jackal. In the neighboring tomb, Robert discovers the corpse of his murdered biological son. He and Jennings are attacked by a pack of dogs and barely escape.
Mrs. Baylock visits Katherine in the hospital and causes her to have an air embolism, killing Katherine. Learning of Katherine's death, Robert goes to Megiddo, meets Bugenhagen, and receives instructions on him to kill Damien on consecrated ground with seven sacrificial daggers. Bugenhagen tells Robert to examine Damien for a birthmark in the shape of three sixes ("666"). However, Robert refuses to kill his son, and throws the daggers on the ground. While reaching down to pick up the daggers, Jennings is suddenly decapitated by a falling sign.
Robert arrives home and is attacked by Mrs. Baylock's Rottweiler, which he subdues. In Damien's room, he finds the 666 birthmark. Mrs. Baylock attacks Robert, but he fends her off; after running her over with his car, he escapes. Pursued by the police, Robert flees to a church to kill Damien, but is found before he can. During his escape, Robert is killed by a Diplomatic Protection officer.
As the Pope simultaneously dies, Robert's funeral is attended by the President of the United States, who holds Damien's hand. Damien then looks at the audience and smiles as the credits roll.
How was the hospital where Damien was delivered demolished?
Fire