When appearing uncredited around two or three films, she began acquiring large roles starting using top featured roles in David O. Selznick's Spellbound (1945), directed by Alfred Hitchcock, and another classic thriller The Spiral Staircase (1946). She so co-starred using Bing Crosby in ''A Connecticut Yankee in King Arthur's Court (1949) based on a book by Mark Twain. Among her best known pic come: Gunfight at the O.K. Corral (1957), While the City Sleeps (1956) and The Big Circus (1959). Within (1953), she starred in Serpent of the Nile and became one of a total of leading Hollywood actresses to play the legendary Egyptian Queen, Cleopatra.

Within retirement she has worked for charities, especially in the field of cancer care, and served on the committees of numerous related bodies. Within 1991 she and her late hubby, Ted Mann, set up a Rhonda Fleming Mann Clinic For Women's Comprehensive Care'' at a UCLA Medical Center. Fleming has the star on the Hollywood Walk of Fame.