Born in 1960 in San Diego, California, RuPaul Andre Charles struggled as a musician and filmmaker in Atlanta, Georgia during the 1980s. He participated in underground cinema, helping create the low-budget Starrbooty (and an album by the same name). In Atlanta, RuPaul often performed at the Celebrity Club as a bar dancer or with his/her band, Wee Wee Pole, which included the late Todd Butler.

In the early 1990s, RuPaul worked the Georgia club scene and was known by his full birth name. Initially participating in "genderfuck"-style performances, RuPaul performed solo and in collaboration with other bands at several New York nightclubs, most notably the Pyramid Club. He appeared for many years at the annual Wigstock drag festival and contributed an appearance to the documentary Wigstock: The Movie. In the '90s, RuPaul was known in the UK for his appearances on the Channel 4 series Manhattan Cable, a weekly series produced by World of Wonder and presented by American Laurie Pike about New York's wild and wacky Public-access television system.

In 1993 RuPaul recorded dance/house albums which included Supermodel of the World. They were released through the hardcore rap label Tommy Boy, spawning the dance track hit "Supermodel (You Better Work)", which was a hit song for RuPaul. The music video was an unexpected success on MTV channels, as grunge-rock (Nirvana) and gangsta rap were popular at the time. The song peaked at #45 on the Billboard Hot 100. The song found the most success peaking at number 2 on the US dance music charts (known as the Billboard Hot Dance Music/Club Play chart). Airplay, heavy rotation of the music video on the MTV network and television appearances on popular programs like The Arsenio Hall Show popularized the song.

His next two songs/videos, "Back to My Roots" and "A Shade Shady (Now Prance)" both went #1 on the Billboard Hot Dance Music/Club Play charts and further developed his campy persona.

RuPaul was signed to a modeling contract for MAC cosmetics, making him the first drag queen supermodel. Various billboards featured him in full drag, often with the text "I am the MAC girl." As well at this time he released his autobiography, Lettin' It All Hang Out. He promoted that book in part with a 1995 guest appearance on ABC's All My Children, in a storyline that put him on the set of Erica Kane's talk show "The Cutting Edge."

The next year he landed a talk show of his own on VH1, called The RuPaul Show, where he interviewed celebrity guests and musical acts. Nirvana, Duran Duran, Pat Benatar, Mary J. Blige, Bea Arthur, Dionne Warwick, Olivia Newton-John, Beenie Man, Pete Burns, Bow Wow Wow, and the Backstreet Boys were notable guests. His co-host was Michelle Visage, with whom he also co-hosted on WKTU radio. On one episode, RuPaul featured guests Chi Chi LaRue and Tom Chase speaking about the gay porn industry. Because of his strong fan base within the gay community, RuPaul has performed at gay pride events and numerous gay clubs. During this time RuPaul helped launch the return of WKTU radio in New York City and would serve as host (with Michelle Visage) of the morning show until 1998.

In 1997, he released a Christmas album entitled Ho, Ho, Ho. He has had guest appearances in many films, including both Brady Bunch movies, in which he played Jan's female guidance counselor. In 1997, RuPaul teamed with Martha Wash to remake the classic disco anthem, "It's Raining Men". The song was included in the 1998 compilation CD RuPaul's Go Go Box Classics, which was a collection of some of his favorite dance songs by other artists. It was during this time that he appeared in Webex TV commercials and magazine ads. In 2001 he recorded with Brigitte Nielsen, credited as Gitta, the Eurodance track You're no lady.

In 2004, RuPaul released his third album, Red Hot, on his own RuCo Inc. label. "Red Hot" showed RuPaul returning to the top of the dance charts in the US with the lead off single "Looking Good, Feeling Gorgeous" hitting number two on the dance chart. The second, "Workout", peaked at number five. The third and final single from the album "People are People" a duet with Tom Trujillo peaked at number 10. The album itself hit only number nine on the Top Electronic Albums chart.

On June 13, 2006, RuPaul released ReWorked, his fifth album. It features reworked versions of songs from his back catalog, as well as new recordings. The only single released from the album is a re-recording of "Supermodel (You Better Work)", reaching number twenty-one on the U.S. dance chart. June 20, 2007 saw the release of "Starrbooty (Original Motion Picture Soundtrack) on iTunes in the US. The single "Call Me Starrbooty" was digitally released in 2007. The album contains new tracks from the singer as well as interludes with dialogue from the movie. The film was released on DVD in October 2007.

In mid 2008, RuPaul began producing RuPaul's Drag Race, a reality television game show which aired on Logo in February 2009. On the show, top drag queens compete to be selected by RuPaul and a panel of judges as the number one drag performer in the country. The winner of Season 1 was Bebe Zahara Benet. One of the contestants, Nina Flowers, was chosen by fans as "Miss Congeniality" through voting on RuPaulsDragRace.com. In publicity preparation for the new show, RuPaul made appearances as a guest on several other shows in 2008 including as a guest judge on Season 5, Episode 6 of Project Runway and as a guest "chef" on Paula's Party.