Portrait photographer Henry Waxman had taken several pictures of Loy, and they were noticed by Rudolph Valentino when the actor went to Waxman’s studio for a sitting. He was looking for a leading lady for Cobra, the first independent project his wife Natacha Rambova and he were producing. Loy tested for the role, which went to Gertrude Olmstead, instead, but soon after she was hired as an extra for Pretty Ladies (1925), in which fellow newcomer Joan Crawford and she were among a bevy of chorus girls dangling from an elaborate chandelier.
Rambova recommended Loy for a small but showy role opposite Nita Naldi in What Price Beauty? (1925). Although the film remained unreleased for three years, stills of Loy in her exotic makeup and costume appeared in a fan magazine and led to a contract with Warner Bros., where her surname was changed from Williams to Loy.
Loy’s silent film roles were mainly as a vamp or femme fatale, and she frequently portrayed characters of Asian or Eurasian background in films such as Across the Pacific (1926), A Girl in Every Port (1928), The Crimson City (1928), The Black Watch (1929), and The Desert Song (1929), which she later recalled “kind of solidified my exotic non-American image.” In 1930 she appeared in The Great Divide. It took years for her to overcome this stereotype, and as late as 1932, she was cast as a villainous Eurasian in Thirteen Women (1932). She also played, opposite Boris Karloff, the depraved sadistic daughter of the title character in The Mask of Fu Manchu (1932).
Prior to that, Loy appeared in small roles in The Jazz Singer and a number of early lavish Technicolor musicals, including The Show of Shows, The Bride of the Regiment, and Under a Texas Moon. As a result, she became associated with musical roles, and when they began to lose favor with the public, her career went into a slump. In 1934, Loy appeared in Manhattan Melodrama with Clark Gable and William Powell. When gangster John Dillinger was shot to death after leaving a screening of the film at the Biograph Theater in Chicago, the film received widespread publicity, with some newspapers reporting that Loy had been Dillinger’s favorite actress.