Booth began her career onstage as a teenager, acting in stock company productions. She was a prominent actress in Pittsburgh theatre for a time, performing with the Sharp Company. Her debut on Broadway was in the play, "Hell's Bells", opposite Humphrey Bogart on January 26, 1925. Booth first attracted major notice as the female lead in the comedy hit "Three Men on a Horse", which ran almost two years from 1935 to 1937. During the 1930s and 1940s, she achieved popularity in dramas, comedies and, later, musicals. She acted with Katharine Hepburn in "The Philadelphia Story" (1939), originated the role of Ruth Sherwood in the 1940 Broadway production of "My Sister Eileen", and performed with Ralph Bellamy in "Tomorrow the World" (1943).