When Kasturba Medical College opened its doors in 1953, it was a single school. The pre-clinical program was located in Manipal, and students had to travel to Mangalore to complete their clinical training at Wenlock District Hospital. In 1955, the first students came to Mangalore to begin their clinical training. This Public Private Partnership (PPP) model was the first of its kind.

In the early stages, Kasturba Medical College in Manipal had two blocks. The Prasanna School of Public Health (PSPH) building housed the medical college nowadays. The physiology block, which currently houses the departments of physiology and pharmacology, was the second block to be erected. Rajkumari Amrit Kaur, the Indian government's then-health minister, dedicated the physiology block.

Considering the construction of a teaching hospital in Manipal was imperative. In 1960, the Medical Relief Society of South Kanara, another charitable organization, volunteered to collaborate with the college to create a sizable hospital in Manipal, providing a favorable opportunity for the establishment of a general hospital in the city. A new, two-story facility housing 150 beds, the freshly built Kasturba General Hospital, marked the beginning of its existence in May 1961.

It became a separate medical institution in 1969 when the clinical program started at Manipal and a full-fledged Kasturba Hospital was established. The Kasturba Medical College has developed into one of the most prominent medical schools in India, continuously ranking in the top five for the past few years. The college hospital has expanded over time to become a super-specialty hospital with 2032 beds. Currently, KMC has graduated students from 56 different nations, and the medical degree (MBBS) is accepted everywhere in the world. Prior to 1993, when the Indian government awarded the Manipal Academy of Higher Education the title of "Deemed University," KMC was governed by Mangalore University.