Wiest was born in the city of Kansas City in the state of Missouri. Anne Stewart (née Keddie), her mother, was a nurse. Bernard John Wiest, her father, was a college dean and a former mental social worker in the United States Army. Her first goal was to be a ballet dancer, but in her final year at Nurnberg American High School, she turned her focus to theater. Wiest earned a degree in Arts and Sciences from the University of Maryland in 1969.
She went on to have a supporting part in Ashes at the New York Shakespeare Festival. She also starred in Henrik Ibsen's "Hedda Gabler" at the Yale Repertory Theatre in New Haven, Connecticut, where she played the lead character.
For "Parenthood" (1989), Wiest was nominated for an Academy Award, and for Bullets over Broadway, she won a Golden Globe. For "Road to Avonlea", she received the 1997 Primetime Emmy Award for Outstanding Guest Actress in a Drama Series, and for "In Treatment" (2008–09), she won the 2008 Primetime Emmy Award for Outstanding Supporting Actress in a Drama Series.
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