The Manhattan Project was the largest, most complex project in human history. The endeavor took place at sites across the United States, Canada, and the United Kingdom, but most of the work occurred at three secret locations. Uranium was enriched at the Oak Ridge Reservation, nestled in the Appalachian valley and ridge province about six miles west of Knoxville, Tennessee. Plutonium was created and processed at the Hanford Reservation, along the Columbia River in southeastern Washington. Nuclear weapons were designed and manufactured at Los Alamos National Laboratory, location of a former boys' school on a remote mesa in New Mexico.

The monumental enterprise to produce nuclear weapons expanded during the Cold War. The Savannah River site, near Aiken, South Carolina, was established in 1950 to increase production of plutonium and tritium for use in nuclear weapons. Lawrence Livermore National Laboratory, built near California farming country, became the Nation’s second weapons-design laboratory to hasten development of the thermonuclear bomb. Plutonium was machined into bomb components at Rocky Flats, Colorado. Nuclear weapons were assembled (and later disassembled) at the Pantex Plant, 17 miles (27 km) northeast of Amarillo, Texas. Altogether the Department of Energy (DOE) weapons complex, as it has come to be known, encompassed more than 100 sites distributed among 31 States and one territory. Individual sites range in size from a few acres to hundreds of square miles. The entire complex covers more than two million acres (800,000 hectares).