Robert Thorn (LIEV SCHREIBER) is an American diplomat living in Italy with his young wife Katherine (JULIA STILES), and the two are expecting their first child. But when Robert rushes to the hospital upon hearing of problems with her labor, he receives the bad news that not only was Katherine's womb damaged and she might not be able to have other children, but also that their infant son has died.
With Katherine still unaware of this turn of events, Robert reluctantly follows the advice of the hospital priest who encourages him to take a recently orphaned infant and accept it as his own, without telling his wife of the switch. Some time later, the happy family is set to move to London where Robert will be the deputy U.S. Ambassador, but he ends up getting the job when his boss meets an untimely demise.
Two years later, all seems well, but the suicide of the family's nanny at young Damien's (SEAMUS DAVEY-FITZPATRICK) birthday party shocks everyone, including press photographer Keith Jennings (DAVID THEWLIS) who's been following Robert's every move. Apparently, so has Father Brennan (PETE POSTLEWAITE), an older priest who urgently warns Robert that his and his wife's lives are in danger -- from their very son.
Robert pays no heed to what sound like the words of a deranged man, and besides, the family's new nanny, Mrs. Baylock (MIA FARROW), has Damien under tight wraps. Nevertheless, Father Brennan continues his warnings, and the presence of seemingly supernatural occurrences eventually begins to give both Robert and Keith second thoughts, particularly with Katherine becoming increasingly spooked by their son and being involved in a near fatal fall caused by him. From that point on, they try to figure out what to do if Damien truly is the Antichrist.