Hayward found employment playing bit parts until she was cast in Beau Geste (1939) opposite Gary Cooper. During the war years, she played leading lady to John Wayne twice in Reap the Wild Wind (1942) and The Fighting Seabees (1944), and the film version of The Hairy Ape (1944).
After the war, she established herself as one of Hollywood's most popular leading ladies in films such as Tap Roots (1948), My Foolish Heart (1949), David and Bathsheba (1951), and With a Song in My Heart (1952).
In 1947, she received the first of her five Academy Award nominations for her role of the alcoholic and fast-rising night-club singer in Smash-Up, the Story of a Woman.
During the 1950s she won acclaim for her dramatic performances as President Andrew Jackson's melancholic wife in The President's Lady (1953); the alcoholic actress, Lillian Roth, in I'll Cry Tomorrow (1955), based on Roth's best-selling autobiography of the same name; and the real-life California killer Barbara Graham in I Want to Live! (1958). Hayward's unglamorous and gritty portrayal of Graham won her an Oscar as Best Actress.