The idea for an International Institute of Intellectual Cooperation, established with the aid of the French government and located in Paris, was first proposed in 1924. It was to provide a permanent secretariat for the League of Nations International Committee on Intellectual Cooperation which aimed to promote international cultural/intellectual exchange between scientists, researchers, teachers, artists and other intellectuals. The Committee was composed of 12 eminent persons (later 19) and met for the first time in the summer of 1922 under the chairmanship of the French philosopher Henri Bergson. Unable to secure the funding required to maintain a significant office in Geneva, the Committee was offered assistance from France to establish an executing agency: the International Institute of Intellectual Cooperation.

The institute was inaugurated with an official ceremony on 16 January 1926. Between 1926 and 1939, the directors of the IIIC were all French. However, the IICI had an autonomous status, separate from the League of Nations and the French Government, and held diplomatic relations with its member states. The states established national commissions for intellectual cooperation and appointed delegates to represent their interests at the Institute in Paris. In 1939, 44 delegates and 45 national commissions worked with the Institute.

The Institute, the national commissions and the delegates of the member states formed an international organization for intellectual co-operation. The organization's structure was confirmed by the International Agreement concerning Intellectual Cooperation, adopted during a conference in Paris in December 1938. The agreement came into effect in the middle of World War II with its eighth ratification in January 1940.

The Institute was closed between 1940 and 1944, but reopened in February 1945, continuing its work until the end of 1946 when UNESCO took over part of its responsibility.