Duff-MacCormick made 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.
In 1976, Duff-MacCormick was nominated for a Drama Desk Award for her portrayal of Julia Craven in George Bernard Shaw's The Philanderer with the Roundabout Theatre Company.
[9] In 1978 she portrayed the role of Hakon's wife in Ibsen's The Pretenders alongside Randall Duk Kim and Stephen Lang at the Guthrie Theater, Minneapolis.
[11] She appeared frequently at the Repertory Theatre of St. Louis during the 1970s, including portraying the roles of Mrs. Sullen in George Farquhar's The Beaux' Stratagem (1976),[12] Bananas in John Guare's The House of Blue Leaves (1977),[13] Judith Anderson in Shaw's The Devil's Disciple (1977)[14] and Sister Rita in The Runner Stumbles (1978).
[21] She returned to the Playwrights Horizons in 1989 to perform the role of Natalie Bauer Lechner in Albert Innaurato's Gus and Al.[22] In 1992, she played Queen Isabella in Christopher Marlowe's Edward II at the Yale Repertory Theatre.