The origin of the Institute dates back to 1973 when the Royal Family of Travancore gifted a multistoried building for the people and Government of Kerala. Sri. P. N. Haksar, the then Deputy Chairman, Planning Commission, inaugurated the Sree Chitra Tirunal Medical Center in 1976, when patient services including inpatient treatment got underway. At the Satelmond Palace, Poojapura, nearly 11 km away from this Hospital Wing, the Biomedical Technology Wing followed soon, again a gift by the Royal Family.

The concept of amalgamating medical sciences and technology within a single institutional framework was regarded as sufficiently important by the Government of India to declare the center as an Institute of National Importance under the Department of Science and Technology by an Act of Parliament in 1980, and named it as Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum.

Dr. Manmohan Singh, the then Honorable Finance Minister of Government of India, laid the foundation stone of the third dimension of the Institute, Achutha Menon Center for Health Science Studies(AMCHSS) on June 15, 1992. Dr. Murali Manohar Joshi, the then Honorable Minister of Science and Technology and Human Resource Development, Government of India, dedicated the AMCHSS to the nation on January 30, 2000.