She portrayed a pickpocket in Ernst Lubitsch's romantic comedy Trouble in Paradise, a bar singer Ivy in Rouben Mamoulian's Dr. Jekyll and Mr. Hyde, and the titular character in the controversial drama The Story of Temple Drake.

When it was adapted as a 1938 film of the same name, Hopkins was bitterly disappointed that Bette Davis was chosen for the role she had played on stage.

She received rave reviews, including one from Mordaunt Hall of the New York Times, saying she portrayed Ivy "splendidly".

In 1932, she made her breakthrough in Ernst Lubitsch's Trouble in Paradise, where she proved her charm and wit as a beautiful and jealous pickpocket.

[9] During the pre-code Hollywood of the early 1930s, she appeared in The Smiling Lieutenant, The Story of Temple Drake, and Design for Living, all of which were box-office successes and critically acclaimed.

Hopkins' early films were considered sexually risqué; produced in the years before the Motion Picture Production Code was rigorously enforced, they featured issues that would be prohibited after 1934.

For instance, The Story of Temple Drake depicted a rape scene, and Design for Living featured a ménage à trois with Fredric March and Gary Cooper.

Her successes continued during the remainder of the decade with the romantic comedy The Richest Girl in the World (1934); the historical drama Becky Sharp (1935), for which she was nominated for the Academy Award for Best Actress; Barbary Coast (1935); These Three (1936) (the first of four films with the director William Wyler); and The Old Maid (1939).

[11] Hopkins auditioned for the role of Scarlett O'Hara in Gone with the Wind; she was the only candidate to be a native Georgian, but the part went to British actress Vivien Leigh.

[citation needed] After Old Acquaintance, Hopkins did not work in films again until The Heiress (1949), where she played the lead character's aunt.

In Mitchell Leisen's 1951 comedy The Mating Season, she gave a comic performance as the mother of Gene Tierney's character.

Her first marriage was to actor Brandon Peters, second to aviator and screenwriter Austin Parker, third to the director Anatole Litvak, and fourth to war correspondent Raymond B.