In 1921, Ayres shot to stardom when she was cast as Lady Diana Mayo, an English heiress opposite "Latin lover" Rudolph Valentino in "The Sheik". Following the release of The Shiek, she went on to have major roles in many other films including The Affairs of Anatol (1921), Forbidden Fruit (1921), and Cecil B. DeMille's epic The Ten Commandments (1923). After her retirement, Ayres became despondent and was eventually committed to a sanatorium. She also lost custody of her daughter to her ex-husband, S. Manuel Reachi, in 1939. She died from a cerebral hemorrhage on December 25, 1940 at her home at the age of 42. For her contribution to motion pictures, Agnes Ayres has a star on the Hollywood Walk of Fame at 6504 Hollywood Boulevard.