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After leaving the pornography industry two days after turning the legal age of eighteen, Lords enrolled at the Lee Strasberg Theater Institute, where she studied method acting with the intention of becoming a mainstream actress. She made her mainstream screen debut at age nineteen in a leading role in the 1988 remake of the 1957 Roger Corman science fiction film Not of This Earth. Lords followed with the role of Wanda Woodward in John Waters' teen comedy, Cry-Baby (1990). Her other acting credits included the television series MacGyver, Married... with Children, Tales from the Crypt, Roseanne, Melrose Place, Profiler, First Wave, Highlander: The Series, Gilmore Girls, and Will & Grace. She also appeared in films such as Skinner (1993), Virtuosity (1995), Blade (1998), Zack and Miri Make a Porno (2008), and Excision (2012), which earned her a Fangoria Chainsaw Award for Best Supporting Actress as well as a Fright Meter Award and a CinEuphoria Award.

Lords also pursued music in addition to her film career. After her song "Love Never Dies" was featured on the soundtrack to the film Pet Sematary Two (1992), she was signed to Radioactive Records and subsequently released her debut studio album, 1000 Fires (1995) to generally positive reviews. Despite the poor sales of the album, the lead single "Control" had moderate commercial success. It peaked at number two on the Billboard Hot Dance Club Songs chart and was included on the soundtrack to the film Mortal Kombat (1995), which was eventually certified double platinum by the Recording Industry Association of America (RIAA). In 2003, Lords published her autobiography, Traci Lords: Underneath It All, which received positive reviews from critics and debuted at number 31 on The New York Times Best Seller list.