Site A was a research facility near Chicago where, during World War II, research on behalf of the Manhattan Project was carried out. Operated by the University of Chicago's Metallurgical Laboratory, it was the site of Chicago Pile-2, a reconstructed and enlarged version of the world's first nuclear reactor, Chicago Pile-1. The first heavy-water reactor, Chicago Pile-3, was also constructed at this site. Research was carried out under contract to the United States' Office of Scientific Research and Development. After the war, the site became the first home of Argonne National Laboratory, a federally funded research and development center.

Chicago Pile-1 (CP-1) was the world's first artificial nuclear reactor. On 2 December 1942, the first human-made self-sustaining nuclear chain reaction was initiated in CP-1 during an experiment led by Enrico Fermi. The secret development of the reactor was the first major technical achievement for the Manhattan Project, the Allied effort to create nuclear weapons during World War II. Developed by the Metallurgical Laboratory at the University of Chicago, CP-1 was built under the west viewing stands of the original Stagg Field. Although the project's civilian and military leaders had misgivings about the possibility of a disastrous runaway reaction, they trusted Fermi's safety calculations and decided they could carry out the experiment in a densely populated area. Fermi described the reactor as "a crude pile of black bricks and wooden timbers".