Dow Medical College (DMC) was founded in 1945, by converting the old medical school of Hyderabad, which was originally started by Dr. Homestead in 1881. Subsequently the College was shifted to function in old N.J.V. High School Building, Karachi, at the beginning of 1946. Dr. Hemandas R. Wadhwani, the Minister of Public Health and Medicine of Sindh Government took keen interest in the establishment of this institution along with Sir Hugh Dow, then Governor of Sindh, helped in establishing this college. The college was subsequently named after him.

Soon after, a new building of the College was constructed within the premises of the School and Civil Hospital was attached as the teaching hospital for the College, and was affiliated to the University of Bombay. After creation of Pakistan, the College was affiliated to Sindh University at Karachi in December, 1947. Subsequently in 1951, when Sindh University was shifted to Hyderabad and Karachi University came into existence, the College was affiliated with Karachi University. In December 2003, Dow University of Health Sciences was created as a University with three constituent institutions, one of which was Dow Medical College.

Since the founding of the College, many additions and improvements have taken place. Today, it is full-fledged institution imparting both undergraduate and postgraduate studies, and has all the departments manned by qualified and experienced staff. It is also one of the largest medical institutions in the country.