Bergner began her career in Zurich in 1919 but reached international fame in Berlin under Max Reinhardt's direction in 1924 of Saint Joan by George Bernard Shaw. Although she was highly regarded as a stage actress—and she continued to perform through the 1960s—it was her motion-picture roles in sentimental romances that gained her the most enthusiastic audience.

Bergner made her first motion picture in 1923; Nju (1924), directed by her husband-to-be, Paul Czinner, was an instant success, as were the films that followed. Denounced by the Nazis, Bergner and Czinner moved to England. Her stage debut there as Gemma Jones in Escape Me Never (1933) was met with great enthusiasm, and she repeated the role in New York City (1935) and again for the film version that was directed by Czinner (1935); the latter performance garnered her an Academy Award nomination. Other English-language films of Bergner's included Catherine the Great (1934), As You Like It (1936), Paris Calling (1942; her only U.S. film), and Cry of the Banshee (1970). Her last motion-picture performance was in 1979.

J.M. Barrie wrote his last play (The Boy David; 1936) especially for Bergner, and she enjoyed a two-season run as Sally in Martin Vale's The Two Mrs. Carrolls (1943). After the war she returned on tour to her homeland on numerous occasions, and there she became the first actress to win the Schiller Prize (1963) for contributions to German cultural life. She also won awards at the Berlin Film festivals of 1963 and 1965.