Vixen was formed in St. Paul, Minnesota in 1980 by guitarist Jan Kuehnemund while still at high school. In 1984, an early version of the band with Kuehnemund, singer Janet Gardner and bassist Pia Maiocco (who later married guitarist Steve Vai) appeared in the movie Hardbodies, as the on-screen band Diaper Rash. In 1985, the band moved to Los Angeles, California to be part of the L.A. rock scene.

Lineup changes happened during the following years until the "classic lineup" of Janet Gardner (lead vocals, rhythm guitar), Jan Kuehnemund (lead guitar), Share Pedersen (bass), and Roxy Petrucci (drums) was formed. This lineup of Vixen was interviewed in 1987 along with many other rock artists of the day by Penelope Spheeris for her film The Decline of Western Civilization II: The Metal Years.

In 1988 the band was signed to EMI, and they began recording their debut album Vixen, which was released in September 1988. Singer-songwriter Richard Marxactually wrote and arranged their signature hit, "Edge of a Broken Heart", as well as performing keyboards and producing the song. Rumor was he was asked to assist the all-female band by EMI to produce their first major-hit, to compete with the all-female band the Bangles. Richard Marxhad nothing to do with their follow-up CD, since he was becoming more of a mainline- singer than songwriter. Vixen spent the next year touring the world, supporting acts such as Ozzy Osbourne, Scorpions and Bon Jovi, as well as headlining their own shows. The band returned to the studio in late 1989/early 1990 to record their follow up album, Rev It Up, which was released in July 1990. A year of touring followed, including headlining their own shows and supporting acts such as KISS and Deep Purple. In mid-1991, the group disbanded due to musical differences.

In 1997, drummer Roxy Petrucci reformed Vixen, with Janet Gardner (lead vocals, rhythm guitar), Gina Stile (lead guitar), and Rana Ross (bass). This lineup toured the United States in 1997, and in 1998 Gardner, Stile, and Petrucci recorded the album Tangerine. After the release of the new album, Roxy's sister Maxine Petrucci was brought in to play bass on a U.S. tour of 1998, but they were sued for copyright infringement by Kuehnemund.

In 1999, Share Pedersen joined her husband's band, the Dogs D'Amour, who were reforming after a long hiatus. She appeared on their 2000 album, Happy Ever After, playing bass, keyboards, and, backing vocals. Share and her husband, Bam, also have their own band, Bubble, which is very popular in L.A..

In 2001, Vixen was reformed by Kuehnemund with a lineup consisting of herself, Janet Gardner, Roxy Petrucci, and new bassist Pat Holloway. This lineup toured the U.S. as part of the Voices of Metal tour. Unfortunately, half-way through the tour, disagreements caused the band to split-up, with only Kuehnemund remaining. Kuehnemund quickly recruited Jenna Sanz-Agero (Jenna Piccolo) (lead vocals), Lynn Louise Lowrey (bass), and Kathrin "Kat" Kraft (drums) to complete the tour. This lineup is still together, and released two new albums in 2006, a live album, recorded at a live show in Sweden, called Extended Versions, and a studio album, Live & Learn.

In 2004, VH1 approached the four members of the "classic lineup" to appear on their show, Bands Reunited. The show was recorded in August 2004, and broadcast in the U.S. in November 2004. Following the broadcast of the VH1 show, EMI re-released the first two Vixen albums, Vixen and Rev It Up.