Born Agnes Hinkle in Carbondale, Illinois, she had planned to have a career in law, but in 1915 at the age of 17 she made her film debut at Essanay Studios in Chicago, and was signed by Fox Studios in 1919. Moving to New York, Ayres gained popularity after being cast in Richard the Brazen (1917), and was signed by Paramount Pictures in 1920.

In 1921, she shot to stardom when she was cast in what is probably her best know role opposite Rudolph Valentino in The Sheik. Ayres played the role for all it was worth, and became the envy of every woman alive as the love interest to the cinema's sexiest new idol. Advertisements and lobby posters showed Ayres' name was top-billed above Valentino's. She went on to have major roles in many other films including The Affairs of Anatol (1921), Forbidden Fruit (1921), and The Ten Commandments (1923), but soon afterward, Agnes' stardom began to decline. In 1926 she reprised her role as Diana in Valentino's Son of the Sheik.

In 1929, Ayres lost her fortune in Crash of ’29, and her career ended with the beginning of talking pictures. Her voice was, according to trade journal reports, improperly pitched for sound pictures. Ayres went successfully into real estate after her film career was over and handled prime Beverly Hills properties.