After five albums with Bongo Maffin she ventured onto a solo career. Her first project, Zabalaza (2004), reached double platinum status and won numerous awards, including a Kora award for Best African Female and four South African Music Awards, including Best Album. It was also nominated for the BBC Radio 3 Planet awards. Her second album, Ibokwe (2009), reached gold status in the first few weeks of its release and her live DVD, Dance of the Forgotten Free (2010), won Best Female Artist and Best Live DVD in 2011. The Guardian has called her “South Africa's finest female contemporary singer.”
Her music is often deeply political and her compositions include traditional Xhosa rhythms, Mbaqanga, reggae, kwaito and funk and jazz sounds.
Thandiswa has performed all over the world at venues, including at the 2010 FIFA World Cup Opening Ceremony, The Apollo in New York, WOMEX, the Cannes Film Festival, Midem, theHackney Empire, Africa Brazil Festival, FESPACO Film Festival, BBC World Music Awards and many Mandela 46664 concerts. She has several noteworthy collaborations. For instance, she collaborated on two songs with US musician Meshell Ndegeocello on her album The World Has Made Me the Man of My Dreams, which was nominated for a Grammy in 2007. At home in South Africa, Thandiswa has collaborated with illustrious musicians including Hugh Masekela, Stimela, the late Busi Mhlongo, and BLK JKS.
In July 2012 she duetted with Paul Simon in Hyde Park, London, in his Graceland album's 25th anniversary concert. She sang the female vocals on Under African Skies, which was originally sung by Linda Ronstadt on the Graceland album.
She is an ambassador for 46664 and an ambassador for the Eastern Cape Province, South Africa