Robert Thorn, portrayed by Liev Schreiber, is an American diplomat stationed in Italy, grappling with a devastating loss. He believes that his son has perished shortly after birth, a tragedy too heavy for his wife, Katherine, played by Julia Stiles, who remains in a state of unconsciousness. To alleviate her pain, Robert agrees to the suggestion of a Catholic priest, Father Spiletto, to clandestinely adopt a newborn whose mother died during childbirth. They raise the adopted child, whom they name Damien, as their own.
As the years pass, Robert's career flourishes, elevating him to the role of Deputy Ambassador to the Court of St. James, and eventually to Ambassador after the previous ambassador meets a suspicious fate. They move into a grand estate outside of London, but as their life appears to take shape, ominous occurrences surround young Damien, played by Seamus Davey-Fitzpatrick. Disturbingly, the most shocking incident occurs at Damien's birthday party when his nanny hangs herself, a tragic act spurred by the presence of a menacing black German Shepherd.
The unsettling events intensify as Robert faces a chilling warning from Father Brennan, a character played by Pete Postlethwaite, who seems to possess unsettling knowledge regarding Damien's origins. Despite the gravity of Brennan’s concerns, Robert dismisses him from his life, but the cryptic nature of his advice lingers. Meanwhile, photographer Keith Jennings observes disturbing anomalies in the photographs he captures, presaging a horrific series of deaths.
To shield Damien, a new nanny named Mrs. Baylock, portrayed by Mia Farrow, enters the household with claims of being sent to protect him. This creates friction with the Thorns as Mrs. Baylock begins to assert her influence over Damien, even introducing a fierce Rottweiler without their consent. On the way to the funeral of the former nanny, Damien displays an alarming reaction when approaching a church, aggressively confronting Katherine.
Katherine's nightmares about Damien begin to plague her, compounded by eerie incidents such as an apocalyptic frenzy among the animals at the city zoo, reinforcing her suspicions that something is gravely amiss with her son. Robert, however, remains skeptical, brushing off her instincts despite the mounting evidence of malevolence.
Faced with the growing pressure and bizarre occurrences, Robert encounters Father Brennan again, who delivers an alarming revelation: Damien must die to fulfill a prophecy. Brennan directs Robert to seek out Bugenhagen in Megiddo for guidance. In a moment of malignant fate, Brennan seeks refuge during a storm but meets a grisly end as a bolt of lightning strikes, leading to his gruesome fate.
When Katherine discovers that she is pregnant, her instinctive fear leads her to consider abortion to prevent another child like Damien. Robert vehemently opposes her wishes, igniting further turmoil. During a seemingly innocent moment, Damien's malice surfaces as he causes Katherine to fall from a height, resulting in a devastating injury and a miscarriage. This traumatic event prompts Robert to finally consider the unsettling truth — there is something dreadfully wrong with his son.
Determined to uncover the truth, Robert collaborates with Keith Jennings and embarks on a quest to find out who Damien's biological mother is. Their investigation leads them to a nun in Rome who reveals the tragic fate of the hospital where Damien was born. The duo's journey takes a darker turn as they encounter Father Spiletto again, revealing crucial details about Damien’s lineage. Their exploration reveals shocking revelations in a cemetery, where they uncover the skeletal remains of a jackal alongside the remains of a human infant, indicating that Damien is not wholly human.
As darkness surrounds their findings, Mrs. Baylock makes her deadly intentions known in the hospital. Disguised as a caring figure, she insidiously causes Katherine's death through devious means. After Katherine's tragic demise, Robert, now fully aware of the depths of horror that his son embodies, sets out to kill Damien, taking the advice of Brennan to heart.
His desperate journey leads him to Megiddo, where Bugenhagen, portrayed by Michael Gambon, confirms that Damien is the Antichrist and offers a path to redemption through sacrificial daggers. Although Robert initially hesitates, he is pushed to take action when Jennings meets a shocking fate, decapitated by a falling sign in a moment of fatal coincidence.
Back at home amidst a raging storm, Robert confronts Mrs. Baylock after discovering the 666 birthmark on Damien. Engaging in a fierce struggle, he fights to rescue his son from the grasp of darkness, running over Mrs. Baylock in a frantic attempt to escape. On a tragic twist of fate, as he stands poised to rid the world of the evil within Damien at a church, Robert is cut down by law enforcement, leaving his tragic mission unfulfilled.
The somber funeral of Robert unfolds coincidentally with the Pope's death, attended by the President of the United States. As the ceremony wraps up, an unsettling scene emerges where the President is seen holding hands with Damien, implying the child has been adopted, concluding with a chilling shot of Damien's diabolical smile aimed directly at the audience, hinting at the darkness that still looms ahead.
