She was discovered in a Little Theater production in 1948. Signed to a seven-year contract with 20th Century Fox, she made fourteen films for the studio. She appeared in five motion pictures for Universal Studios, including the cult film It Came From Outer Space. Released on May 27, 1953, the sci-fi feature was adapted from the writing of Ray Bradbury. It was Universal's first entry into the 3D-film medium. Hughes co-starred with Edward G. Robinson in a 1953 crime drama, The Glass Web, and opposite Rock Hudson in an adventure film that year, The Golden Blade.

On July 25, 1954, Hughes married Stanley Rubin, the Producer of Bracken's World, at the home of her uncle. The couple has one daughter and three sons. The marriage lasted 59 years, until Rubin died on March 2, 2014 from natural causes at the age of 96.

By 1956, she was appearing in television series. She played in episodes of Alfred Hitchcock Presents (1956–1957), Telephone Time (1956), The Bob Cummings Show (1958), The Adventures of Ozzie and Harriet, 77 Sunset Strip (1959), Hotel de Paree (1959), Tightrope (1959), General Electric Theater (1960–1962), The Tall Man (1961), Bachelor Father (1962), Gomer Pyle, U.S.M.C. (1965), and I Dream of Jeannie (1967).

In 1962, Hughes played the role of murder victim Lita Krail in the 6th season, 1962 episode of Perry Mason, entitled "The Case of the Double-Entry Mind". She played the recurring role of Mrs. Coburn on the television series The Ghost & Mrs. Muir. She appeared on M*A*S*H as Lorraine Blake, wife of unit commander Henry Blake, in a home movie she sent to him. Hughes portrayed Mitch, a secretary, on the NBC drama Bracken's World (1969-1971).