She appeared in a number of successful plays in New York like East is West, The Willow Tree, and Dodsworth. In 1926 she appeared with Walter Abel in a Broadway production of Channing Pollock's The Enemy. In 1918, her portrait was painted by Robert Henri, the Ashcan School artist.
MGM persuaded her to try films and her movie debut was in This Side of Heaven (February 1934), the same year she appeared inDodsworth on Broadway and the film It Happened One Day (July 1934). Bainter quickly achieved success, and in 1938 she became the first performer nominated for both the Academy Award for Best Actress, for White Banners (1938), and the Academy Award for Best Supporting Actress for Jezebel (1938), winning for the latter. Since then, only nine other actors have won dual nominations in a single year. She was again nominated for Best Supporting Actress for her role in The Children's Hour (1961). Finally, in 1962, Fay appeared as a guest star on The Donna Reed Show.
She has a star on the Hollywood Walk of Fame at 7021 Hollywood Boulevard in Hollywood
Fay Bainter and Reginald Venable married on June 8, 1921, in Riverside, California. The couple had one son, Reginald Venable Jr. (1926–1974), who became an actor. Bainter was the aunt of actress Dorothy Burgess.
As her husband, Reginald Venable, was a military officer, the couple are interred at Arlington National Cemetery.