In 1943 she starred in Home in Indiana, and in 1944 in In the Meantime, Darling. Her acting in the latter film was critically panned, but she rebounded in the hit Winged Victory in the same year. In 1945 she starred in State Fair, and in 1949 in three films, A Letter to Three Wives, The Fan and Pinky, for which she was nominated for the Academy Award for Best Actress. Pinky was a controversial movie, since it told the story of a girl who passes for white in the northern United States. Although Lena Horne and other black actresses were considered for the role, Darryl F. Zanuck chose to cast a white actress for box-office reasons.
Roles became fewer in the 1950s as Crain went into semi-retirement to raise a family. Her last role was in Skyjacked in 1972.