MCHS was formed by a merger of the Lilongwe School of Health Sciences (LSHS) in Lilongwe, the Medical Assistants Training School (MATS) in Blantyre and Zomba School of Nursing (ZSN) in Zomba. The merger of the three campuses was established through a government order, dated 21 June 1996.

The Lilongwe School of Health Sciences, formerly known as the Medical Auxiliary Training School, was built in 1976. The school opened its doors on 12 July, 1976. The initial classroom infrastructure was built with funding from the French Government. Later, the Howard University Project constructed the administration block and some hostels. More students hostels were erected by the World Bank under the Population, Health and Nutrition (PHN) project. The World Health Organisation (WHO), under "the essential drug programme", donated some equipment and rehabilitated a laboratory to facilitate teaching and learning.

The Medical Assistants Training School in Blantyre became operational in the 1960s. However, the present structure was built in 1996 with funding from the African Development Bank (ADB).

The Zomba School of Nursing which opened in 1930 is the oldest institution. The current structure was built in 1990 with support from the World Bank under the Population, Health and Nutrition (PHN) project.

Until 1996 the three schools operated separately under the MoHP. MCHS is now an autonomous parastatal organisation under a Board of Governors. The Government of the United Kingdom, through its Department of International Development (DFID), is assisting the MCHS in improving its academic and administrative functions over a period of five years, from 1999 to 2004.