In the city of Jerusalem, Israel, just a week following the interment of Robert and Katherine Thorn from the first Omen film, archeologist Carl Bugenhagen (Leo McKern) persuades his acquaintance Michael Morgan (Ian Hendry) to transport a mysterious box to the custodian of Thorn's young son, Damien. Bugenhagen reveals the foreboding truth—that Damien is none other than the Antichrist and that the box contains both a warning and the means to end Damien's life. Although skeptical, Morgan's disbelief wanes after Bugenhagen takes him to the ruins of Yigael's wall, where an ancient depiction surfaces, showing the Antichrist bearing Damien's likeness. Tragically, their exploration is cut short when the tunnel they occupy collapses, burying them alive.
Fast forward seven years, and the now 12-year-old Damien (Jonathan Scott-Taylor) resides with his uncle, the affluent industrialist Richard Thorn (William Holden) and his aunt Ann (Lee Grant) in a sprawling residence just outside Chicago, Illinois. Damien has formed a bond with his 15-year-old cousin, Mark (Lucas Donat), with whom he shares enrollment at a military academy. Meanwhile, his Aunt Marion (Sylvia Sidney) is openly hostile towards him, considering him a negative influence on Mark and even threatens to disinherit Richard if he doesn't keep the boys apart. One fateful night, disturbed by the eerie presence of a raven, Marion suffers a heart attack and dies.
Through a connection with Dr. Charles Warren (Nicholas Pryor), the curator of the Thorn Museum, Richard encounters journalist Joan Hart (Elizabeth Shepherd), linked to the prior events through her association with Keith Jennings. After witnessing the ominous relation between the depictions on Yigael's Wall and the string of suspicious deaths surrounding Damien, Joan attempts to warn Richard, only to be dismissed and ejected from his car. From that point on, her inquiries lead to grim fates; an encounter with Damien prompts a panic-stricken escape, resulting in a horrific accident involving a raven and a truck.
Months later at Thorn Industries, manager Paul Buher (Robert Foxworth) proposes an ethically questionable expansion into agriculture, but is swiftly rebuffed by senior manager Bill Atherton (Lew Ayres). At Mark's birthday celebration, Buher introduces himself to Damien, revealing his plan for initiation. A series of tragic accidents claim the lives of those opposing Buher—raising suspicions as the dark presence of the raven continues to loom.
At the military academy, Sgt. Dan Neff (Lance Henriksen) advises Damien to remain inconspicuous until the moment is right, pointing him towards Chapter 13 of Revelation. As Damien discovers the ominous number 666 marked on his scalp, a wave of terror overtakes him, leading to his flight from the academy.
Bad omens continue when an explosion at the factory leads to fatalities and leaves Damien unscathed, much to the bewilderment of Dr. Kane. Upon investigating Damien's unusual blood structure, a tragic accident soon claims the doctor as well. Meanwhile, Bugenhagen's box resurfaces, revealing the Seven Daggers of Meggido, the only weapons capable of taking Damien's life, and a letter confirming his identity as the Antichrist. But when Charles attempts to share this alarming discovery with Richard, he is met with disbelief and thrown out.
Tensions escalate when Mark discovers Damien's true nature during a heated confrontation, leading to a horrifying end where Damien kills him using his sinister powers. Heartbroken and desperate, Richard journeys to New York City, where he is finally confronted with the undeniable truth when Bugenhagen's warnings manifest tragically again.
Returning home, Richard confronts Ann, but she, revealed to be complicit, ultimately uses the daggers against him. In a fiery finale, with every adversary vanquished, Damien emerges as the sole heir to Thorn Industries and savors his ascent under the dark guidance of nefarious figures like Sgt. Neff and Paul Buher, signaling his dominion over a world destined to align with the evil he embodies.
