Clayton's first film was When the Earth Trembled. Following appearances on screen in short dramas from 1909 to 1912, she made her feature-length film debut in For the Love of a Girl in 1912. Barry O'Neil directed the film, and Clayton later was directed by William Demille, Robert G. Vignola, George Melford and Donald Crisp in subsequent feature films. Like many silent film actors, Clayton's career was hurt by the coming of sound to motion pictures. She continued her career in small parts in films until she retired in 1948.