Born Edythe Marrenner in Brooklyn, New York of Irish American and Scandinavian extraction, she began her career as a photographer's model. She was a school friend of the actor and fellow Brooklynite, Jeff Chandler. She went to Hollywood in 1937, aiming to become the unknown who won the role of Scarlett O'Hara in Gone with the Wind.

Although she didn't get that role, Hayward landed a few bit parts until she eventually landed the female lead in Beau Geste (1939) opposite Gary Cooper which made her a superstar. During the war years, she played leading lady to John Wayne twice in Reap the Wild Wind and The Fighting Seabees. Post-war, she established herself as one of Hollywood's most popular leading ladies in films such as Tap Roots, My Foolish Heart, David and Bathsheba, and With a Song in My Heart.

In 1947 Hayward received the first of her five Academy Award nominations for Smash-Up, the Story of a Woman. Other major films included I'll Cry Tomorrow and I Want to Live!, for which she won the Oscar as Best Actress.

She appeared in a Las Vegas production of Mame for which she initially received good reviews for her charming performance, but for which role she was vocally unprepared, and she blamed herself for not having wanted to spend the money on voice lessons that might have allowed her to keep the role. Loretta Swit played "Agnes Gooch" in the same production.

After Hayward was forced to withdraw from the production, she was replaced by the talented, but prickly, singer/actress Celeste Holm. Hayward warned Holm that if she mistreated the "great" company she was now joining, then she (Hayward) would "kick your a** back to Toledo", from whence Holm did not even come.

Susan Hayward is also remembered for appearing at the 1974 Oscar telecast to present the award for Best Actress, despite the fact she was dying of cancer. With Charlton Heston gallantly supporting her, and having been given massive doses of dopamine, she managed to get through it. Hayward later stated, "that's the last time I do that". Hayward met Katharine Hepburn for the first time at the telecast, and Hepburn served as a kind of booster urging Hayward to fight her cancer.

Susan Hayward died on March 14, 1975, of pneumonia-related complications coinciding with her brain cancer following a fierce battle that Hayward waged against her disease, refusing to give in, just as she had refused to do so many times during her life in almost any given situation. She was 57 years old.