Myers left for New York City, where she acted mainly in theater for the next two years. She was signed by Universal, where she emerged as a popular actress in vamp roles. Her most popular film from this period—which does not feature her in a vamp role—is probably the romantic comedy All Night, opposite Rudolph Valentino, who was then a little-known actor. She also worked with him in A Society Sensation. By 1924, she was working for Metro-Goldwyn-Mayer, making such films as Broadway After Dark, which also starred Adolphe Menjou, Norma Shearer, and Anna Q. Nilsson.
In 1925, she appeared in arguably her most famous role, that of the Egyptian vamp Iras in Ben-Hur: A Tale o the Christ, who tries to seduce both Messala (Francis X. Bushman) and Ben-Hur himself (Ramon Novarro). This film was a boost to her career, and she appeared in major roles throughout the 1920s, including Tell It to the Marines in 1926 with Lon Chaney, Sr., William Haines, and Eleanor Boardman. Myers appeared in Four Walls and Dream of Love, both with Joan Crawford in 1928; and in The Show of Shows (1929), a showcase of popular contemporary film actors.