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Charlton Heston, Roy Scheider, Dick Van Dyke, and William Holden turned down the lead role. Gregory Peck, accepted the lead. William Holden starred in the sequel Damien: Omen II (1978). Heston starred in an Omen-like film The Awakening (1980) where the film's plot (similar to The Omen) involved the unearthing of an evil Egyptian princess which possesses his daughter from childbirth.
Harvey Stephens, as Damien, was largely chosen for this role from the way he attacked Richard Donner during auditions. Donner asked all the little boys to "come at him" as if they were attacking Katherine Thorn during the church wedding scene. Stephens screamed and clawed at Donner's face, and kicked him in the groin during his act. Donner whipped the kid off him, ordered the kid's blond hair dyed black and cast him as Damien.
Mrs. Baylock was originally written as a warm, effusive Irish nanny. For her audition, Billie Whitelaw significantly changed the dialogue to create the cold, slightly sinister character that subsequently appeared in the film.
According to at least one biography of Gregory Peck, he took this role at a huge cut in salary (a mere $250,000) but was also guaranteed 10% of the film's box office gross. When it went on to gross more than $60 million in the U.S. alone, it became the highest-paid performance of Peck's career.
(at around 1h 4 mins) The taxi driver who takes Thorn around Italy was the son of a Mafioso in real life and was very keen to get into the movies. In one scene, he can quite clearly be seen sporting a large bandage on his thumb - this was because Gregory Peck had accidentally slammed a car door on his hand, nearly taking off his finger.
One of the reasons why Gregory Peck accepted the role of a tortured father, conflicted with guilt, was because he hadn't been around when his son Jonathon committed suicide in 1975.