The Manhattan Project was a research and development undertaking during World War II that produced the first nuclear weapons. It was led by the United States with the support of the United Kingdom and Canada. From 1942 to 1946, the project was under the direction of Major General Leslie Groves of the U.S. Army Corps of Engineers. Nuclear physicist Robert Oppenheimer was the director of the Los Alamos Laboratory that designed the actual bombs. The Army component of the project was designated the Manhattan District as its first headquarters were in Manhattan; the placename gradually superseded the official codename, Development of Substitute Materials, for the entire project. Along the way, the project absorbed its earlier British counterpart, Tube Alloys. The Manhattan Project began modestly in 1939, but grew to employ more than 130,000 people and cost nearly US$2 billion (equivalent to about $23 billion in 2020). Over 90 percent of the cost was for building factories and to produce fissile material, with less than 10 percent for development and production of the weapons. Research and production took place at more than thirty sites across the United States, the United Kingdom, and Canada.

Two types of atomic bombs were developed concurrently during the war: a relatively simple gun-type fission weapon and a more complex implosion-type nuclear weapon. The Thin Man gun-type design proved impractical to use with plutonium, and therefore a simpler gun-type called Little Boy was developed that used uranium-235, an isotope that makes up only 0.7 percent of natural uranium. Since it was chemically identical to the most common isotope, uranium-238, and had almost the same mass, separating the two proved difficult. Three methods were employed for uranium enrichment: electromagnetic, gaseous and thermal. Most of this work was performed at the Clinton Engineer Works at Oak Ridge, Tennessee.

In parallel with the work on uranium was an effort to produce plutonium, which was discovered by researchers at the University of California, Berkeley, in 1940. After the feasibility of the world's first artificial nuclear reactor, the Chicago Pile-1, was demonstrated in 1942 at the Metallurgical Laboratory in the University of Chicago, the Project designed the X-10 Graphite Reactor at Oak Ridge and the production reactors at the Hanford Site in Washington state, in which uranium was irradiated and transmuted into plutonium. The plutonium was then chemically separated from the uranium, using the bismuth phosphate process. The Fat Man plutonium implosion-type weapon was developed in a concerted design and development effort by the Los Alamos Laboratory.

The project was also charged with gathering intelligence on the German nuclear weapon project. Through Operation Alsos, Manhattan Project personnel served in Europe, sometimes behind enemy lines, where they gathered nuclear materials and documents, and rounded up German scientists. Despite the Manhattan Project's tight security, Soviet atomic spies successfully penetrated the program. The first nuclear device ever detonated was an implosion-type bomb at the Trinity test, conducted at New Mexico's Alamogordo Bombing and Gunnery Range on 16 July 1945. Little Boy and Fat Man bombs were used a month later in the atomic bombings of Hiroshima and Nagasaki, respectively, with Manhattan Project personnel serving as bomb assembly technicians, and as weaponeers on the attack aircraft. In the immediate postwar years, the Manhattan Project conducted weapons testing at Bikini Atoll as part of Operation Crossroads, developed new weapons, promoted the development of the network of national laboratories, supported medical research into radiology and laid the foundations for the nuclear navy. It maintained control over American atomic weapons research and production until the formation of the United States Atomic Energy Commission in January 1947.