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After debuting both off and on Broadway in 1977, followed by her television debut as Nola Dancy Aldrich on the NBC soap opera The Doctors (1978–1979), Turner rose to prominence with her portrayal of Matty Walker in Body Heat (1981), which brought her a reputation as a sex symbol. She worked solidly throughout the 1980s in films such as The Man with Two Brains (1983), Crimes of Passion, Romancing the Stone (both 1984), Prizzi's Honor, The Jewel of the Nile (both 1985), Switching Channels, The Accidental Tourist (both 1988), and The War of the Roses (1989). For her portrayal of the title character in Peggy Sue Got Married (1986), Turner was nominated for the 1987 Academy Award for Best Actress. Subsequent credits include V.I. Warshawski (1991), Serial Mom (1994), Baby Geniuses, The Virgin Suicides (both 1999), Beautiful (2000), Marley & Me (2008), and Dumb and Dumber To (2014).

Outside film, Turner guest-starred as Sue Collini on Showtime's Californication (2009) and Roz Volander on Netflix's The Kominsky Method (2019–2021). She also played Charles Bing, the drag queen father of Chandler Bing, on the seventh season of Friends (2001). Turner's voice work includes Jessica Rabbit in Who Framed Roger Rabbit (1988) and Constance in Monster House (2006), as well as characters on television series such as The Simpsons, Family Guy, King of the Hill, and Rick and Morty.

In addition to her work on stage and screen, Turner has taught acting classes at New York University.