Pitchblende was thought to be a ore with zinc, iron and tungsten. However, in 1789, the German chemist M. S. Klaproth discovered a new element in pitchblende ores which he named uranium in honor of the planet Uranus, which had been discovered just eight years before. The French scientist Henri Becquerel discovered the radioactive property of uranium in 1896.

Enrico Fermi and his coworkers observed in 1934 that the bombardment of uranium by neutrons produced beta radioactivity, although the full significance of this observation was not understood at the time. In 1938, Otto Hahn and Fritz Strassmann showed that when uranium was bombarded by thermal neutrons it fissioned into radioactive isotopes of lighter elements, such as krypton and barium, and that part of the binding energy holding the protons and neutrons together in the heavy uranium nucleus was released. In 1939, at a conference in the United States, Fermi suggested that when uranium nuclei are split under neutron bombardment other neutrons might also be released in sufficient number to cause a continuous self-sustaining fission reaction. The existence of these fission neutrons was confirmed in 1939 in studies by F. Joliot, Leo Szilard, H.L. Anderson and their coworkers.

The first self-sustaining nuclear chain reaction was achieved by Fermi and a team of scientists in a pile of 400 tons of graphite, six tons of uranium metal and 58 tons of uranium oxide, at the University of Chicago, on December 2, 1942.

The first test of a nuclear explosive device occurred on Alamogordo, New Mexico, on July 16, 1945 and the first nuclear weapon was used in warfare August 6, 1945, at Hiroshima.