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Born Mary Elizabeth Hughes in Alton, Illinois, Hughes’ parents divorced in 1923. After the divorce, Hughes’s mother, Mary Frances Hughes (née Lucas), moved with her only child to Washington, D.C. As a child, Hughes began acting in stage productions. While acting in a school play in the early 1930s, her performance caught the attention of Clifford Brown, a repertory theater company owner, who offered her a part in a touring production of Alice in Wonderland. While touring with another production in Brown’s company, she was offered a contract from a talent scout with Gaumont-British Studios but declined the offer to finish high school.  Upon graduating from high school in 1937, she returned to Brown’s theater company, where she continued to appear in various stage productions until the summer of 1938, when she relocated to Los Angeles with her mother to pursue a film career. After six months of failing to land movie roles, Hughes and her mother made plans to return to Washington, D.C., until Hughes met an agent, Wally Ross. Ross introduced Hughes to powerful William Morris agent Johnny Hyde. Hyde landed Hughes a contract with MGM, and she soon landed a small, uncredited role in the 1939 film Broadway Serenade.

After Broadway Serenade, Hughes appeared in other bit parts in films including The Women with Norma Shearer, Dancing Co-Ed with Lana Turner, and the Busby Berkeley film Fast and Furious.  In 1940 Hughes was offered a contract with 20th Century-Fox. Later that year she landed a role opposite John Barrymore in The Great Profile, a part she later noted as one of her favorites. Fox did not renew her contract when it expired in 1943, and the following year she began appearing in a nightclub act and soon signed a three-picture deal with Universal Pictures.  Her most famous role was as Henry Fonda’s former girlfriend in the Best Picture Academy Award nominee, The Ox-Bow Incident (1943). Throughout the mid-40s and early ’50s, Hughes appeared in film and television roles, including the cult classic I Accuse My Parents (which was later parodied on Mystery Science Theater 3000), Waterfront at Midnight, Wanted: Dead or Alive (episode “Secret Ballot”),The Devil’s Henchman, The Abbott and Costello Show, Dragnet and Studio One.

In 1961, Hughes decided to retire from acting and began working as a receptionist in a plastic surgeon’s office, although she continued her appearances in nightclubs. The following year she directed and starred in a Los Angeles production of Pajama Top. For the rest of the ’60s she would go on to appear in television shows like Rawhide and Dennis the Menace. In 1970 she landed a regular role on The Red Skelton Show, appearing in 11 episodes before the show ended later that year. In 1976 she again retired from show business, explaining that she was “tired of auditioning for sexy grandma roles.” Hughes’ last onscreen appearance was in the 1976 film Tanya.  In the late 1970s Hughes opened a beauty parlor in Canoga Park, California. She closed the shop in the late 1980s and began working as a telemarketer until 1991, when she was laid off.

As a starlet under contract with MGM, Hughes went on studio-appointed dates with several actors, including Lew Ayres, Franchot Tone, Mickey Rooney, and James Stewart. While under contract to Fox, she also went on prearranged dates with Milton Berle and George Montgomery.  In 1940, against Fox’s wishes, Hughes began a relationship with actor Robert Stack. The romance lasted a year.  After her romance with Stack ended, Hughes married actor Ted North in 1943. The couple had one son, Donald, before divorcing in 1947. In 1948, she married singer/actor David Street. The marriage ended in 1956. In 1973 Hughes married her manager, Nicky Stewart, but that marriage also ended in divorce four years later.  Mary Beth Hughes died at the age of 75 on August 27, 1995, of natural causes in Los Angeles.