Carlisle's first venture into music was a brief stint as drummer for the punk band The Germs, under the name Dottie Danger, although illness prevented her from ever performing with them live. Soon after leaving this band, she founded The Go-Go's (originally named The Misfits), with friend and fellow music novice Jane Wiedlin. With bassist-turned-guitarist Charlotte Caffey, guitarist-turned-bassist Kathy Valentine, and drummer Gina Schock, the Go-Go's became one of the most successful American bands of the early 1980s, helping usher new wave music into popular American radio, and becoming the first all-female band in rock history to ever achieve a #1 album, who also wrote their own music, and played their own instruments.

The Go-Go's broke up in 1985, and Carlisle embarked on a solo career (although she continued to work with fellow Go-Go Charlotte Caffey). Carlisle's first album, Belinda, was released on I.R.S. Records, in 1986. Her #3 Summer hit "Mad About You" was followed by the Motown-influenced single "I Feel the Magic", and by a cover version of "Band of Gold". All three songs were included on her debut album. During this time, Carlisle also had songs featured on movie soundtracks, notably "In My Wildest Dreams," the opener in the movie Mannequin, as well as "Dancing in the City" from the Whoopi Goldberg movie Burglar.

Carlisle changed her hairstyle significantly for her second solo album, giving up her California Girl blonde bob for a long auburn doo for 1987 Heaven on Earth. The musical style eschewed the 1960s-influenced pop of Carlisle's first album in favor of slickly produced 1980s power-pop, and was released in the United States through MCA, and in the United Kingdom through Virgin. The album became a Top 5 bestseller in the UK and Australia, and was nominated for a Grammy Award. The first release from Heaven on Earth was the semi-title track "Heaven Is a Place on Earth", which topped the single charts, not only in the U.S., but also in the UK and Australia.

Carlisle's follow-up to the success of Heaven on Earth was Runaway Horses, released on October 23, 1989. The album again hit the Top 5 in both Australia and the UK, certified double platinum in Australia and platinum in the UK, but failed to reach similar success in the U.S. Whereas in the U.S. Carlisle's success was decreasing, her popularity remained big in Europe and Australia.

In 1991, Carlisle released her fourth solo album, Live Your Life Be Free. The album marked somewhat of a return to 1960s-influenced music for Carlisle. Carlisle broke her contract with MCA, her U.S. record company, in 1992. Still active in Europe and Australia with a record contract at Virgin Records, her 1992 greatest hits album, The Best of Belinda, Volume 1, reached #1, and was certified double platinum in both the UK and Australia. This first greatest hits album of her included all the hits taken from the Heaven on Earth, Runaway Horses, and Live Your Life Be Free albums.

Carlisle's fifth solo album, Real, was released in 1993, on the Virgin label, in the U.S. and in Europe. Produced without Nowels, the disc was a departure from Carlisle's polished pop music formula. Gone was her glamorous image and picture-perfect pop too. Even the album's cover photograph featured her with very little make-up, which perfectly matched the album title. Carlisle co-produced and co-wrote much of the disc, collaborating heavily with friend and former Go-Go's member Charlotte Caffey. The album reached #9 in the UK, and its first single, "Big Scary Animal", peaked at a respectable #12 placing in the UK.

In 1996, Belinda released in the UK and Australia her sixth solo album, A Woman and a Man, on the Chrysalis Records label. This album, consisting of mostly relaxed adult pop, revitalized her solo career in Europe, and included several hits. The leadoff single, "In Too Deep", returned Carlisle to the UK Top 10, for the first time in six years, reaching #6. The album reached #12 in the UK, and was certified gold.

In 2007, the singer released her seventh album Voilà, which was her first solo full-length studio album in over ten years (though The Go-Go's definitively reunited in 2001, and released their fourth full-length studio album that year, God Bless the Go-Go's, the follow-up to 1984 Talk Show). Consisting of a mix of French pop tunes and chanson standards, including covers of Françoise Hardy and Édith Piaf classics, Voilà was released via Rykodisc in the UK on February 5, and in the U.S. the following day, February 6, 2007.