The foundation stone of the college was laid on 29th May 1957 by the then Governor of Kerala Dr.B.Ramakrishna Rao. The College was formally inaugurated on the 5th August 1957 by the then minister of Health, Dr.A.R.Menon whose initiative and zeal were responsible for the establishment of the institution. The task of organising the college was in the capable hands of Dr.K.N.Pisharady, the first Principal. With the completion of the college building in 1959 the preclinical section was shifted from the temporary location to the campus. The main collegiate hospital with 1183 beds was commissioned in 1966 and the Institute of Maternal and Child Health with 610 beds was commissioned in 1975.
The Savithri Devi Saboo Memorial Cancer Institute with 101 beds, an artificial limb centre and casualty complex are additions to the institution. Later on the Chest Hospital, Samraksha Kendram and Vishrama Kendram were added. New blocks for the College of Nursing and College of Pharmacy are the recent additions. A superspeciality complex is under construction.
From its modest beginning the institution has grown steadily for the last 41 years. The annual intake of undergraduate students was increased from 50 to 200. The consolidation of undergraduate [medical education was achieved in the 1960's and the 1970's witnessed the establishment and expansion of postgraduate medical education in the various branches of medical science. With the establishment of training programmes in the superspecialities, the institution further widened its academic horizon. During the last decade almost all modern specialty services in medical care have been developed in the institution facilities for Kidney Transplant and Whole Body Scan. A well equipped Cath Lab and Tele Cobalt Therapy are recent additions to the hospital complex. . A well equipped Medical Education Unit was also started . The Dental College which was earlier attached to Medical College has been separated and is functioning independently. The college also conducts in Nursing, Pharmacy, Lab technician training, training of Radiological Assistants and Ophthalmic Assistants. MSc.Nursing was started in the College of Nursing during 1997. The Medical library and most of the departments of the college have been provided with computer facility.
The Calicut Medical College also boasts of a strong Alumni Association. The Calicut Medical College Alumni Association takes active role in the academic and co-curricular advancements. The Alumni association supports the Calicut Medical Journal.
See also History of Medical Education in Calicut.