The college's original building was built before the Partition of Bengal of 1905. As of 1904, the building was being used as the secretariat (headquarters) of the newly formed provinces of East Bengal and Assam. In 1921, it was turned over to the University of Dhaka, which was founded that year. A part of the huge building was used as the university's medical center, another part as the students' dormitory, and the rest as the office of the administrative wing of the Arts faculty.
In 1939, the Dhaka university council requested that the British Government establish a separate medical college in Dhaka. The proposal was postponed because of the onset of the Second World War.
During World War II the medical center building became an American armed forces hospital. The Americans vacated the building at the end of the war.
Finally, Dhaka Medical College was established in 1946, and the college began admitting students. Academic classes started on 10 July which is celebrated as "DMC DAY". The 1st year, beginning class, or "Batch", was named K-5, 2nd year K-4, 3rd year K-3, 4th year K-2, and 5th year K-1. All the advanced students (K-4 through K-1) had transferred from the Calcutta Medical College, in large part because of the partition of India.