In the late 1930s, at the beginning of World War II, researchers at the University of Chicago's Metallurgical Laboratory (Met Lab) and their affiliates at the Argonne National Laboratory in nearby Lemont, Illinois were charged with researching atomic energy. Though not officially involved in the war until December 1941, the U.S. government feared the repercussions of atomic research done by scientists in Nazi Germany and so began to develop its own atomic weapons program.  

The Met Lab, led by Enrico Fermi and Arthur Compton, built an atomic reactor and on December 2, 1942 used the reactor to successfully achieve a controlled nuclear reaction. The reactor, known as CP-I (Chicago Pile-I) was discharged in a chamber underneath the University of Chicago's Stagg Field. Nuclear Energy, sculpted by Henry Moore, was dedicated in 1967 to mark the 25th anniversary of the reaction. 

The reactor was later moved from the University of Chicago to the Argonne Lab, where it was renamed CP-II. The research done at the Met Lab, the Argonne Lab, and at other Manhattan Project sites, including Hanford, Washington, was used to develop the atomic bombs used to end Japan's involvement in World War II.  

Met Lab scientists warned the U.S. government of the potentially devastating effects of nuclear war. They formed the Atomic Scientists of Chicago and used their influence to try and guide U.S. government policy regarding atomic weapons. The U.S. government's use of atomic bombs in Hiroshima and Nagasaki and its Cold War-era nuclear program suggest that these warnings fell on deaf ears.  

The site was designated a Chicago Landmark in 1971.