Preferring the stage, she did not appear in many films, and in Hollywood she was considered a character actress who was difficult to cast because of her striking features. She received an Academy Award nomination for Best Supporting Actress for her role in Alfred Hitchcock's Rebecca (1940). As the housekeeper "Mrs. Danvers", Anderson was required to mentally torment the young bride played by Joan Fontaine, even encouraging her to commit suicide, and the character is widely considered to be one of the screen's most memorable and sexually ambiguous female villains.
This led to several film appearances during the 40s in such films as Kings Row (1943), Laura (1944), The Diary of a Chambermaid (1946). She continued returning to the New York stage, playing the role of Lady Macbeth twice and winning a Tony Award in 1948 for her historically acclaimed bravura performance in the title role of Medea (play).
In her later years she played two more prominent roles in productions that took her as far away from her Shakespearean origins as possible. In 1984 she appeared in Star Trek III: The Search for Spock as the Vulcan High Priestess (at the age of 87), and the same year commenced a three year stint as matriarch Minx Lockridge on the popular soap opera Santa Barbara of which she had professed to be a fan, but bitterly complained about her lack of screen time after signing the contract. She was succeeded in the role by the American actress, Janis Paige, who was a quarter of a century younger.