Whilst living in Italy, American diplomat Robert Thorn (Peck) is persuaded to substitute a newborn baby whose mother has died in childbirth for his own stillborn son. By the age of five Damien (Harvey Stephens) seems to be exerting a malevolent influence on the Thorn household, suffering a violent fit when he is taken to church and causing his nanny to hang herself.

Thorn searches for an answer to his son's behaviour and meets maverick priest Father Brennan (Patrick Troughton), who tries to convince him that Damien is in fact the Antichrist and must be stopped at all costs. At first dismissive of the priest, Thorn soon comes to believe that he may have been right after all...