In 1942 an unofficial Provisional Committee was set up in Jamaica to make plans for a local University College. Philip Sherlock was nominated as one of the promoters. In 1943, with the blessings of the Vice-Chancellors of the United Kingdom Universities, a special commission was set up under a High Court Judge, Sir Cyril Asquith, (later known as the Asquith Commission) to consider the principles which guide the promotion of higher education, learning and research and the development of universities in the colonies.

The Asquith Commission appointed Sir James Irvine, Vice-Chancellor of the University of St. Andrews, as Chairman for the West Indies Committee. At the same time the Legislative Council in Jamaica passed a resolution in favour of the formation of a regional university. In 1945 the Secretary of State accepted and recommended the Irvine Report which was in favour of the Council's resolution. The Council selected a site at Mona in St. Andrew, as an appropriate site for the College.

Dr. Thomas Taylor, a noted Biochemist, was appointed as the first Principal. While the Mona Campus was under construction, Dr. Taylor opened the first office of the University College of the West Indies at 62 Lady Musgrave Road, Kingston, on February 1, 1947. The opening of the office was a starkly simple affair, with three or four prayers read in the presence of Dr. Taylor's wife, Georgina; Philip Sherlock, the only other member of the Faculty; Sylvia Dunkerly, the sole Secretary and the College's first driver, George Errar.

Early in 1947, the University College relocated to Gibraltar Camp at Mona which had been the site of a camp for refugees from Gibraltar and Malta as well as German and Italian prisoners of war. October 3, 1948 saw the official opening of the Mona Campus with ten females and twenty-three males from across the region entering the fledgling University in the Faculty of Medicine.

Natural Sciences followed in October, 1949 and the Faculty of Arts in October, 1950.

By 1950, UC as the College was affectionately called, was well established at Mona. The 304 students in residence included 138 who were studying medicine, 65 in the Faculty of Natural Sciences, 85 in Arts and 16 in Education. There were only 80 women in the group.

In 1960 the St. Augustine Campus of the University College of the West Indies was born out of the former Imperial College of Tropical Agriculture. The Cave Hill Campus was established in 1963 to train those interested in Law.

On April 2, 1962 the University College of the West Indies became the University of the West Indies under the Great Seal of the Realm, with Princess Alice, Princess of Athlone, as the first Chancellor and Sir Arthur Lewis as the first Vice-Chancellor. The University was now a degree granting institution.