Amphlett grew up in Geelong, Australia as a singer and dancer. She left home as a teenager and travelled to England, France and Spain—she was imprisoned for three months in the latter country for singing on the streets.
In May 2001, Divinyls' "Science Fiction", written by Amphlett and lead guitarist Mark McEntee, was selected by the Australasian Performing Right Association (APRA) as one of the Top 30 Australian songs of all time. Amphlett and McEntee barely spoke after the band separated in 1996, but resumed contact when they were inducted in 2006 into the ARIA Hall of Fame—the pair eventually announced a new tour and album. Amphlett died in 2013 after a long battle with breast cancer and multiple sclerosis
Amphlett met Mark McEntee at a concert at the Sydney Opera House in 1980, and with Jeremy Paul (Air Supply), they formed Divinyls. After several years performing in Sydney, they recorded several songs for the film Monkey Grip, in which Amphlett also acted.
Divinyls consisted of an ever-changing lineup formed around Amphlett and McEntee, whose relationship was always volatile. Nevertheless, the band released six albums between 1982 and 1996, peaking in 1991 with the success of their single "I Touch Myself", which reached Number 1 in Australia, Number 4 in the USA, Number 10 in the UK. Divinyls did not release another album for six years, breaking up around the time of Underworld's release in Australia. Amphlett lived in New York City with her husband, concentrating on a solo career and writing her autobiography, Pleasure and Pain: My Life.
Amphlett and McEntee barely spoke after the band broke up, but resumed contact when they were inducted in the 2006 ARIA Hall of Fame and eventually announced a new tour and album. They recorded and released a single, "Don't Wanna Do This", and toured Australia, but the proposed reunion album was never made.
Amphlett performed Divinyls' and other songs with a 30 piece orchestra for the Australian Rock Symphony in January 2010.
In 2011, she released the single "Summer Song" under the name The Tulips, a band consisting of Amphlett, Charley Drayton and Kraig Jarret Johnson. It was used in the soundtrack for the film The Music Never Stopped.
Amphlett also worked as an actress, making her film debut in Monkey Grip (1982) in a supporting role as the temperamental lead singer of a rock band. Monkey Grip's author, Helen Garner, claimed that the film's director preferred Amphlett in the role of Jane Clifton as "Clifton was neither good looking enough or a good enough singer to play herself."
Amphlett played Judy Garland in the original touring production of The Boy from Oz, with Todd McKenney playing the role of Peter Allen. When the highly successful show transferred to Broadway in the year 2000, Garland was played by American performer Isabel Keating and Allen by Hugh Jackman. On its return to Australia as an arena spectacular, Amphlett resumed playing the role.
Amphlett grew up in Geelong and attended Belmont High School. She was a cousin of Australian singer Little Pattie (Patricia Amphlett).
Amphlett and her bandmate Mark McEntee were romantically involved from 1982 to 1993. They had met in 1980, and began a relationship two years later when McEntee had split up with his wife. Their relationship was highly volatile—marred with drug and alcohol use, and physical fights—however the band's manager, Vince Lovegrove, later stated that the nature of their "weird" relationship was the "magic of Divinyls".
On 27 July 1999, Amphlett married American drummer Charley Drayton, who played drums on the Divinyls' eponymous album and was the drummer in the reformed group.
In an interview on the Nine Network program A Current Affair, on 7 December 2007, Amphlett revealed that she had multiple sclerosis. On 20 October 2010, she announced that she had breast cancer and was being treated in New York where she lived with her husband. She also said that her sister is a breast cancer survivor. On 24 January 2011, she claimed to be free of cancer.
Amphlett died, aged 53, on 21 April 2013 at her home in New York City, US after a long battle with breast cancer. Due to the multiple sclerosis that Amphlett concurrently suffered from, she reported that she was unable to receive radiation treatment or chemotherapy as cancer treatment. Following the announcement of Amphlett's death, numerous tributes were received from artists, performers and musicians—Crowe wrote: "RIP Chrissie Amphlett, [she] played my mum in Blood Brothers, 1988."