Chadwick was born in Macclesfield and was educated at the University of Manchester, where he graduated in 1911 and remained as a graduate student under Ernest Rutherford. In 1913 he went to Leipzig to work under Hans Geiger and found himself interned in 1914 near Spandau as an enemy alien. There he remained for the duration of the war, cold and hungry but permitted, with the help of Walther Nernst, to carry out rudimentary research.

On his return to England in 1919 he was invited by Rutherford to accompany him to Cambridge University where, from 1922 until 1935, he served as assistant director of research at the Cavendish Laboratory. It was during this period that Chadwick, in 1932, made his greatest discovery – the neutron. Before this, physicists had accepted the existence of only two elementary particles: the proton (p) with a positive charge, and the electron (e) with a negative charge. It was however clear to all that these two particles could not account for all the atomic phenomena observed. The helium atom, for example, was thought to consist of four protons; that it only possessed a positive charge of two was due to the nucleus also containing two ‘internal electrons’, which neutralized the charge on two of the protons. The difficulty of such a view was the failure of a disintegrating nucleus to produce the electrons supposedly contained within it.

In 1920 Rutherford had provided an alternative solution by introducing the possibility of “an atom of mass 1 which has zero nuclear charge.” Chadwick attempted unsuccessfully to discover such a particle in the 1920s by bombarding aluminum with alpha particles (helium nuclei). More promising, however, was the report in 1930 that the bombardment of beryllium with alpha particles yielded a very penetrating radiation. In 1932 Irène and Frédéric Joliot-Curie found that this radiation could eject protons with considerable velocities from matter containing hydrogen. They thought such radiation consisted of gamma rays – electromagnetic radiation of very short wavelength. Chadwick showed that the gamma rays would not eject protons, but that the result was explained if the particles had nearly the same mass as protons but no charge, i.e. the particles were neutrons. It was for this work that Chadwick was awarded the 1935 Nobel Prize for physics.

By 1936 a certain amount of friction had begun to appear between Chadwick, who wished to build a cyclotron at the Cavendish Laboratory, and Rutherford who initially was violently opposed to any such project. It was therefore with some relief that Chadwick decided in 1935 to accept the offer of the chair of physics at Liverpool University. There he built Britain's first cyclotron and was on hand at the outbreak of war to support the claims made by Otto Frisch and Rudolph Peierls on the feasibility of the atomic bomb. Chadwick consequently spent most of the war in America as head of the British mission to the Manhattan project.

For this service he was knighted in 1945. He returned to Cambridge in 1958 as Master of Gonville and Caius College, in which office he remained until his retirement in 1958.