Her first small part in the cinema was in 1918, in Thirty a Week. She acted on the New York stage as well: her first starring role was in 39 East. In 1923 she moved to England for several years and was very popular. Her success led to a contract with Paramount studios in Hollywood, but she was not a major success. She went back to New York and the legitimate stage. Her biggest success was in 1939 with The Little Foxes, and in 1942 with Skin of our Teeth. Her 1944 film Lifeboat was her best. She turned to television in the '50s with the early and very successful talk show The Big Show.
Bankhead was famous for her outrageous behavior on and off stage; she had problems with alcohol and drugs. Although she was married to John Emery for four years, she was bisexual. Her last years were spent in largely unsuccessful attempts to make a comeback on the stage.