The first Sisters of Mercy arrived in Cape Town, South Africa, in October 1897. They opened the first Convent of Mercy in Mafeking, in February 1898. Mercy has been present in that country ever since. In 1994 the Sisters of Mercy in South Africa joined the 26 Irish Mercy congregations to form the Congregation of Sisters of Mercy (Ireland) of which they are now a province.

At present, Sisters of Mercy from three Mercy families live and minister in South Africa: the Congregation of Sisters of Mercy (Ireland), Sisters of Mercy of the Union of Great Britain and the Institute of the Sisters of Mercy of the Americas.

Ministry of the Sisters of Mercy in South Africa is rich and varied. It includes health care in the form of wellness clinics, HIV/AIDs clinics, a dental clinic, nutrition clinics, and the provision of other support for people who face the consequences of HIV/AIDs. Education ministry includes skills development centres, teaching, a music centre, catechetics, and other support for children and parents. There are shelters for homeless women and children, as well as a shelter for abused and trafficked women. Some sisters engage in retreat and spiritual direction ministry, prison visitation, and providing support in human development. There are small business development programmes and a couple of social services advice bureaus. In addition, sisters are involved in the care of orphans and vulnerable children, support of seasonal workers who face high levels of unemployment, provision of refugee services, and the running of a centre for justice.