Born in Woodstock, Ontario, Duff-MacCormick studied acting at the American Academy of Dramatic Arts in New York City before making her professional debut Off-Broadway in December 1969 at the Cherry Lane Theatre as Faith Detweiler in Harold J. Chapler's Love Your Crooked Neighbor. She made her Broadway debut as Shelly in Michael Weller's Moonchildren in 1972, a role she had performed the year before at the Arena Stage in 1971.

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