The 1980s saw Hughes rise as one of Australia's most prolific and versatile actresses. She was an aspiring croupier who leaves her con artist lover in "Hoodwink" (1981) and caused something of a stir as a doomed insurance investigator in "A Dangerous Summer" (1982), in that audiences didn't expect an actress of her position would be killed off so early in the film. Paul Cox cast her against type as the dowdy, sexually-repressed spinster who finds romance in "Lonely Hearts" in 1982. Despite that triumph, though, Hughes had one of her best screen roles ever as the wealthy Anglophile engaged in a custody battle for her nephew in "Careful, He Might Hear You" (1983), for which she earned the Best Actress prize from the Australian Film Institute. Cox again coaxed a terrific performance from the actress in "My First Wife" (1984), in which she essayed a cheating wife who is caught by her husband. Some felt her one misstep was accepting the part of an incompetent psychiatric nurse in "An Indecent Obsession" (1985). She bounced back with the soap opera-ish role of a woman who becomes disgusted with her philandering husband and finds romance with a folk dancer (John Lone) in "Echoes of Paradise" (1987) and a woman of loose morals in "Boundaries of the Heart" (1988), which also marked her debut as an associate producer. Hughes additionally added screenwriting to her resume with the comedy "Luigi's Ladies" (1989).

After acting in the apocalyptic ABC miniseries "Amerika" in 1987, Hughes and her family relocated to L.A. to try to pursue a career in Hollywood, but American producers seemed not to know how to use this performer's gifts. She co-starred with Pierce Brosnan in the HBO movie "The Heist" (1989) and proved effective as the mother of the future first lady in "A Woman Called Jackie" (NBC, 1991), but roles with the depth and breadth of those to which she was accustomed in Australia remained elusive. Hollywood cast her as brothel madam in the execrable "Wild Orchid II: Two Shades of Blue" (1992) and she had a one-season (1993-94) recurring role as a medical examiner on NBC's "Homicide: Life on the Street".

Returning Down Under, Hughes anchored the TV series "Snowy River: The McGregor Saga" (1993-95) and reunited with Paul Cox for a gender-bending turn in "Lust and Revenge" (1996). She went on to play one of the female inmates in "Paradise Road" (1997) and won acclaim for her starring role in the 1997 Australian TV series "State Coroner". In 2001, Hughes reunited with former co-stars Judy Davis and Colin Friels for the romantic comedy "The Man Who Sued God" and returned to the stage playing Mrs. Robinson in the Australian premiere of the stage version of "The Graduate".