The colleges were established as a single institution in 1953 by T M A Pai with the pre-clinical section at Manipal and the clinical section in Mangalore at Wenlock District Hospital. Manipal and Mangalore were then a part of the erstwhile Madras state. The government of Madras granted land to establish a college and permitted the use of government hospitals for training medical students. The first batch of students arrived in Mangalore in 1955 for their clinical training. In 1956, the colleges became part of the expanded Mysore state which was then renamed as Karnataka.^[1]

The clinical program commenced at Manipal in 1969 with the setting up of Kasturba Hospital. The colleges were later separated with the establishment of a pre-clinical section in Mangalore. Kasturba Medical College, Mangalore is attached to three government hospitals and was the first medical institution in India to be established as a public-private partnership.^[2]