With the surname of her husband, Dolores would make her debut in the movie "Joanna", directed by Carewe in 1925. Hollywood first noticed her appeal as a sex siren, but she struggled against the "Mexicali Rose" image initially pitched to her by Hollywood executives. Despite her brief appearance, Carewe performed an exhaustive publicity for the actress. In her second film High Steppers, Dolores took the second female credit after Mary Astor. His films were not blockbusters, but helped increase the popularity of Dolores. The real intention of Carewe was transforming Dolores into a female version of Rudolph Valentino. In late 1926, director Raoul Walsh called Dolores to give her a role of the movie What Price Glory. With the character of Charmaine, Dolores achieved her desired success. Later, she was selected as one of the WAMPAS Baby Stars in 1926 (along with fellow newcomers Joan Crawford, Fay Wray, Janet Gaynor, and Mary Astor). She came to be admired as one of the most beautiful women on screen. After she gained fame, Carewe produced Resurrection, which was a box office hit.
In 1927, Raoul Walsh called Dolores to star in its second version of Carmen (the first was with Theda Bara). The Dolores's career flourished until the end of the silent era, with successful films such as Ramona (1928), and Evangeline (1929). But while Dolores's career was flourishing, her marriage declined. Jaime had little success in Hollywood. Jealous of his wife and frustrated, Jaime left, after fleeing to Germany, where he committed suicide in 1929. The arrival of the talkies, forced a painful leaving of the custody of Carewe, who made several charges against her. With the support of United Artists, Dolores manages to escape the harassment of Carewe and debuted in the talkies with The Bad One in 1930.
In 1930, she married Cedric Gibbons, one of MGM's leading art directors and production designers, whom she met at a party organized by the businessman William Randolph Hearst and his lover, the actress Marion Davies in the fortress of Saint-Simeon. With the advent of talkies, she was usually relegated to exotic and unimportant roles. Carewe tried revenge on her in 1931 with a new version of Resurrection with her rival, Lupe Velez, without success. Dolores scored successes with Bird of Paradise (1932, directed by King Vidor) (the film scandalized audiences when she turned out swimming stark naked with Joel McCrea), Flying Down to Rio (the film that launched the careers of Fred Astaire and Ginger Rogers) (1933) and Madame DuBarry (1934), Wonder Bar (1934) and the Busby Berkeley comedies In Caliente (1935) and I live for love (1935).
In the late thirties, Dolores's career began to experience a decline. With the support of Warner Bros., she made a series of police films (such as Lancer Spy in 1937) without success. For awhile she was marked as "box office poison", along with some comrades like Marlene Dietrich, Joan Crawford, Katharine Hepburn and others.
In 1940, Dolores met Orson Welles, who at that time was up & coming in Hollywood. Feeling a mutual attraction, the pair began a torrid romance. Welles fell madly in love with her, although he was 10 years younger. The affair was reported to have been the cause of her divorce from Gibbons in 1941. Dolores was with Welles for two years, during he which left his career. She was at his side during the filming of Citizen Kane, and stood with him during the attacks of Randolph Hearst against him. She collaborated with Welles in the film Journey into Fear in 1943. After the breaking of Welles with RKO, Dolores sympathized with him, though her character (a sexy leopard-woman) in the film, was reduced.