Gayle was born in London, and attended the Barbara Speake stage school in Acton, west London, where Naomi Campbell, Amma Asante and Kwame Kwei-Armah were among her contemporaries. She first became publicly known when she appeared in the children's BBC television programme Grange Hill in 1988 and 1989 as Fiona Wilson, who was most notably part of a rap duo named Fresh 'n' Fly.

Gayle later appeared as an extra in TV Drama London's Burning and in the Children's ITV television programme Press Gang in 1990 as a background member of the news team, and that same year she won the role of Hattie Tavernier in the popular BBC soap opera EastEnders. The introduction of the Tavernier family heralded the first time that an entire family had joined the programme all at once. Their introduction was also a well-intentioned attempt to portray a wider range of black characters than had previously been achieved on the show. Gayle's character remained in the show for three years as Ian Beale's PA and was featured in an array of storylines including being abandoned by her fiancé Steve Elliot (Mark Monero) and suffering a miscarriage as a result. However, music was always Gayle's first passion, and in 1993 she left EastEnders to pursue a singing career.

Before she gained commercial success, Gayle sang with a rap duo called R-MOR-FUS, performing gigs at various clubs and low-key venues. In 1993, while she was still on the cast of EastEnders, Gayle signed with RCA Records and launched herself as a solo Artist. She scored a number 11 hit with her debut single "Looking Up". By 1994, she had her biggest-selling single to date, "Sweetness", which reached number 4, spent 16 weeks in the UK Singles Chart and was certified silver, selling more than 300,000 copies. Gayle had further chart success in 1994 with the number-26 hit "I'll Find You"; in 1995 with the number-16 "Freedom"; and the number-11 "Happy Just to Be With You" which sampled Chic's Good Times. These five singles were taken from Gayle's self-titled debut album Michelle Gayle, which was released in 1994, peaked at number 30 in the UK Albums Chart, and was certified gold.

Gayle also appeared on the Childliners charity record "The Gift of Christmas" in 1995, alongside acts such as Backstreet Boys, Boyzone, E.Y.C., Sean Maguire, Deuce, Ultimate Kaos, Let Loose, East 17, Peter Andre, MN8, Dannii Minogue and many more. It peaked at number 9.

Gayle returned in 1997 with her sixth single, "Do You Know", which reached number 6. This was followed by the song "Sensational", which reached number 14. Both singles were taken from Gayle's second album, Sensational. Despite Sensational being praised by critics, the album had disappointing sales. It entered the album chart at number 17, but quickly fell out of the top 40 the following week. Due to poor album sales, Gayle left RCA. During the time she was signed to the label, Gayle received three BRIT Award nominations: two in 1995 for 'Best Single' and 'Best Female Artist', and one in 1998 for 'Best Female Artist'.

Following her departure from RCA, Gayle signed with EMI. She recorded an album for that label, but due to an Artist rostering re-shuffle, she had left the company by 1999 before the album was released. After leaving EMI in 1999, Gayle took to the West End stage and played Belle in Disney's Beauty and the Beast. After an extended break from showbusiness to look after her son, Isaiah, Gayle began developing her music production company M Media Productions. She also appeared on other artists' albums, including that of Ivan Matias, Me One, Shabba and Lemon D.

In 2003, Gayle accepted the offer to appear in the reality television series Reborn in the USA, a televised singing competition where former British pop acts were transported to the USA, with the hope of revitalising their music careers. Gayle finished second in the competition, taking runner-up position to Tony Hadley in the final. Following her success on the programme, Gayle began working on new material.

Gayle was a contestant on ITV's reality-television show Reborn in the USA, competing against artists such as Elkie Brooks, Sonia, Gina G, Leee John and Tony Hadley. Gayle made it to the final and finished second behind Hadley. In 2004, Gayle presented the UMA Awards with ex-EastEnder Gary Beadle, and in 2005, she appeared as a Celebrity mentor on the Five documentary Pushy Parents.

In March 2006, she took part in the fourth series of the Channel 4 reality-television show The Games competing against various other celebrities in a series of Sports events. Gayle came third in the competition and raised more than £5,000 for her chosen charity, the Willow Foundation. She later became a guest panellist on ITV's topical chatshow Loose Women, in June 2007.

During an interview with the Blackpool Gazette in February 2007, Gayle mentioned that she was in the process of writing her first novel. The plot involved an unpleasant TV talent-show judge who discovers he is dying. She said: "It's sort of fiction but not fiction but it is made up and true, so when you read it you'll see it's fictional but also real, and I hope it explains a few things about the pop Business.". It was never published.

Gayle was married to ex-professional footballer and football pundit Mark Bright for 10 years, and had one son, Isaiah, with him. The couple separated in 2007. They officially divorced on 18 April 2008. Gayle is godmother to the daughter of the Actress Jacqui Gordon-Lawrence, who played her on-screen mother, Etta Tavernier, in EastEnders. Gayle is a teetotaller and doesn't eat meat. On 4 August 2011 it was announced on The Wright Stuff that she was pregnant. On Twitter, she announced the birth of her son, Luke, on 2 November 2011.

In June 2009, it was announced that Gayle would be one of several celebrities competing in Dancing on Wheels, BBC's spin-off show to the popular reality television competition Strictly Come Dancing. Dancing on Wheels paired able-bodied celebrities with those in wheelchairs. The winning pair represented the UK at the Wheelchair Dance Sport European Championships in Israel in October 2009. Gayle and partner Harry Maule reached the semi-finals, but were beaten in the dance-off by Diana Morgan-Hill and Olympic Swimmer Mark Foster.

Walker Books acquired the rights to Gayle's novel, Pride and Premiership, in 2010 and the book was published on 5 May 2011. The novel, aimed at a teen market, depicts the story of two girls who aspire to be WAGs, or wives/girlfriends of football players. Gayle, who was once married to a professional footballer, has commented, "In the time of Jane Austen’s Pride & Prejudice a woman had to get married to support herself. We’ve got to an age where a woman can support herself but still wants to marry a footballer to support her. I’m not WAG-bashing or footballer-bashing, I just want girls to make informed decisions about their Future."

Gayle reinvented herself as a UK R&B Artist, and worked on material for her third album with New York record Producer Terence Dudley — famous for working on 50 Cent's album Get Rich or Die Tryin'. At the end of 2004, Gayle appeared on several TV shows promoting the release of her new single, "Gotta Be Me", but the single was pulled before its release. In an interview with The Voice newspaper in April 2006, Michelle divulged that she did make a new album, but her record company (N2 Records) folded.

In March 2018, she begun playing the role of as Alison in the musical Son of a Preacher Man, which is based on the life of Dusty Springfield.