The Institute for the Study of Ancient Cultures was founded in 1919 by James Henry Breasted with the financial support of John D. Rockefeller Jr., and was originally envisaged as a research laboratory for the investigation of the early human career that would trace humankind’s progress from the most ancient days of West Asia and North Africa. The goal of the Institute for the Study of Ancient Cultures is to be the world’s leading center for the study of the ancient civilizations of West Asia and North Africa by combining innovation in theory, methodology, and significant empirical discovery with the highest standards of rigorous scholarship.

The Institute for the Study of Ancient Cultures Museum was opened to the public in 1931. The majority of ISAC's collections are from its expeditions in West Asia and North Africa during the 1920s, 1930s, and 1940s. A major reinstallation of the Museum, including the construction of a climate-controlled wing for housing collections and archives, took place in the 1990s and early 2000s. A complete renovation of the Museum was completed in 2019 in celebration of ISAC's centennial. The Institute for the Study of Ancient Cultures is a unit within the University of Chicago and the name of the corporation is “The University of Chicago.” The corporation was originally incorporated on September 10, 1890.