Frédéric Joliot, the son of a prosperous Paris tradesman, was educated at the School of Industrial Physics and Chemistry. In 1923 he began his research career at the Radium Institute under Marie Curie, where he obtained his doctorate in 1930. He was appointed to a new chair of nuclear chemistry at the Collège de France in 1937 and, after World War II in which he played an important part in the French Resistance, was head of the new Commissariat à l'Energie Atomique (1946–50. In 1956 he became head of the Radium Institute.

In 1926 Joliot married the daughter of Marie Curie, Irène, and changed his name to Joliot-Curie. In 1931 they began research that was to win them the Nobel Prize for chemistry in 1935 for their fundamental discovery of artificial radioactivity (1934). His description of the crucial experiment is as follows: “We bombarded aluminum with alpha rays [the heavy nucleus of a helium atom, made of two protons and two neutrons] … then after a certain period of irradiation, we removed the source of alpha rays. We now observed that the sheet of aluminum continued to emit positive electrons over a period of several minutes.” What had happened was that the stable aluminum atom had absorbed an alpha-particle and transmuted into an (until then) unknown isotope of silicon, which was radioactive with a half-life of about 3.5 minutes. The significance of this was that it produced the first clear chemical evidence for transmutation and opened the door to a virtually new discipline. Soon large numbers of radioisotopes were created, and they became an indispensable tool in various branches of science. Dramatic confirmation of the Joliot-Curies' discovery was provided when Frédéric realized that the cyclotron at the laboratory of Ernest Lawrence in California would have been producing artificial elements unwittingly. He cabled them to switch off their cyclotron and listen. To their surprise the Geiger counter continued clicking away, registering for the first time the radioactivity of nitrogen–13.

In 1939 Joliot-Curie was quick to see the significance of the discovery of nuclear fission by Otto Hahn. He confirmed Hahn's work and saw the likelihood of a chain reaction. He further realized that the chain reaction could only be produced in the presence of a moderator to slow the neutrons down. A good moderator was the heavy water that was produced on a large scale only in Norway at Telemark. With considerable foresight Joliot-Curie managed to persuade the French government to obtain this entire stock of heavy water, 185 kilograms in all, and to arrange for its shipment to England out of the reach of the advancing German army.