Lee has appeared on a variety of television shows such as The Robin Byrd Show in 1977, the Howard Stern Show in 1991, and more recently The Bill Cunningham Show in 2011. She has appeared in minor roles such as the 1994 thriller Killing Obsession. In 2013 she appeared in an episode of the Showtime Cable network's After Dark television series Gigolos.

After winning the Miss Nude Galaxy contest in Roselawn, Indiana in 1979 (and again in 1981), its owner cast Lee in The Young Like It Hot (1983). Her movie debut happened in Naughty Girls Need Love Too, also from 1983.

In 1984, she appeared in Sweet Young Foxes. In that same year she appeared in Penthouse magazine, in the same September record-breaking best-selling issue that featured Miss America 1984, Vanessa Williams.

Over time, her husband Bud Lee joined the cast and crew of her films. Together they created the second-most-expensive pornographic film (at the time), The Ribald Tales of Canterbury (1985), with Bud directing and Hyapatia starring and screenwriting a version of Geoffrey Chaucer's The Canterbury Tales.

For SRO Records, Lee recorded the 7" single, "Telephone Man", released in 1988; and the album Two Sides Of Hyapatia Lee in 1989. "Rub-a-Dub-Dub" from the album featured on Dr. Demento's 'Funny Five' playlist, airing April 30, 1989.

She views Hyapatia as a particular personality that allowed her to perform. She met and married Bud Lee, with whom she bought land in rural southern Indiana, where she has lived since. The couple had two children, whom she homeschooled at their Indiana home. In 1993 she retired from the industry and separated from Bud the same year. She has since remarried and had another child.

In 1994, Lee recorded the album Double Euphoric with her band W4IK. She toured with the same band, which was based in Los Angeles, and also with another band, based in Indiana, called Vision Quest.

In 1998, members of her fan club received a report that she had died due to diabetes. The report was inaccurate.

In 1999, one of Lee's tracks from her 1994 release appeared on the music CD Porn to Rock.

In 2000, Lee self-published an autobiography, The Secret Life of Hyapatia Lee. In 2016, she authored a self-help book, Native Strength – The First Step on the Path to an Indomitable Life, the first in a series. She has subsequently put out four additional Native Strength self-help books.

Double Euphoric was re-released in September 2010, both in physical and digital versions, via outlets such as CD Baby, Amazon and Apple iTunes.

In December 2017, her documentary Native Strength – Pilot Episode, the first in a series, was shown at the Mile Hi Mocs and Docs Film Festival in Denver, Colorado.