After working briefly as a model, Kirkland trained at the Actors Studio and began performing in off-Broadway productions. It would take appearing nude in the 1968 Terrence McNally play "Sweet Eros," however, for Kirkland to make a real impact.
After supporting roles in films such as The Sting (1973) and Private Benjamin (1980), Kirkland received a Best Actress Oscar nomination for playing the titular character in Anna (1987). More recent films include 2003's Bruce Almighty.