Ms. Sisulu was appointed as Minister of Tourism on 5 August 2021. She was Minister of Human Settlements, Water and Sanitation from 30 May 2019 to 5 August 2021. She was Minister of International Relations and Cooperation from 27 February 2018 to 25 May 2019. Ms Lindiwe Nonceba Sisulu was the Minister of Human Settlements of the Republic of South Africa from 26 May 2014 until 26 February 2018.

She has been a Member of Parliament since 1994. She has been chairperson of the Inaugural of the African Ministerial Conference on Housing and Urban Development since 2005. Ms Sisulu is member of the National Executive Committee of the African National Congress (ANC) and a member of the National Working Committee of the ANC. She was a trustee of the South African Democracy Education Trust; trustee of the Albertina and Walter Sisulu Trust; and a member of the Board of the Nelson Mandela Foundation.