Fassie was born in Langa, Cape Town, as the youngest of nine children. She was named after the American singer Brenda Lee. Her father died when she was two, and with the help of her mother, a pianist, she started earning money by singing for tourists.
In 1981, at the age of 16, she left Cape Town for Soweto, Johannesburg, to seek her fortune as a singer. Fassie first joined the group Joy and later became the lead singer for a township music group called Brenda and the Big Dudes. She had a son, Bongani, in 1985 by a fellow Big Dudes musician. She married Nhlanhla Mbambo in 1989 but divorced in 1991. Around this time she became addicted to cocaine and her career suffered.
With very outspoken views and frequent visits to the poorer townships of Johannesburg, as well as songs about life in the townships, she enjoyed tremendous popularity. Known best for her songs "Weekend Special" and "Too Late for Mama", she was dubbed "The Madonna of the Townships" byTime in 2001.
In 1995 she was discovered in a hotel with the body of her lesbian lover, Poppie Sihlahla, who had died of an apparent overdose. Fassie underwent rehabilitation and got her career back on track. However, she still had drug problems and returned to drug rehabilitation clinics about 30 times in her life.
From 1996 she released several solo albums, including Now Is the Time, Memeza (1997), and Nomakanjani?. Most of her albums became multi-platinum sellers in South Africa; Memeza was the best-selling album in South Africa in 1998