She created the role of Rose in the original Broadway production of Elmer Rice's Pulitzer Prize-winning play Street Scene (1929), and was put under contract in Hollywood and made a number of films in the 1930s.

[6] She was the star of Elmer Rice's Street Scene (1929), a naturalistic drama about life in a New York City tenement that ran for 601 performances on Broadway, toured throughout the United States, and received the Pulitzer Prize.

[7] Her other films include Dangerous Corner (1934), Little Men (1934), His Greatest Gamble (1934), Seven Keys to Baldpate (1935), Streamline Express (1935), Our Little Girl (1935), Two in the Dark (1936), The Ex-Mrs. Bradford (1936), Ring Around the Moon (1936), The Leavenworth Case (1936), Green Light (1937) and The Plough and the Stars (1937).

[8] Described by The New York Times as "a slender, dark-haired woman with fragile, beautiful features", O'Brien-Moore had a rising career that was interrupted by severe injuries she suffered January 22, 1939, in a fire.

[10]: 596 [citation needed] Her later feature films include Destination Moon (1950), The Family Secret (1951), Sea of Lost Ships (1954), Phantom of the Rue Morgue (1954), Peyton Place (1957) and How to Succeed in Business Without Really Trying (1967).