The laboratory was founded as the University of California Radiation Laboratory in 1931 by Ernest Orlando Lawrence, a University of California Berkeley physicist who won the 1939 Nobel Prize in physics for his invention of the cyclotron, a circular particle accelerator that opened the door to high-energy physics. It is a United States Department of Energy National Laboratory, operated by the University of California. The name of the laboratory has evolved since its founding: Lawrence Radiation Laboratory (1931-1958), the Lawrence Berkeley Laboratory (1959-1995), and currently the Lawrence Berkeley National Laboratory (1995-present).

The 60-inch Cyclotron accelerated its last beam on Saturday, June 30, 1962. It began operation on the same day in 1939, 23 years earlier. After the shutdown, the cyclotron was dismantled and shipped to the University of California, Davis, where it became the basis of a new spiral-ridge accelerator. The 60-inch cyclotron had been the site of many important developments, including the creation of seven new elements; the creation, production and distribution of artificial radioisotopes; tracer experiments; treatment and control of disease; and studies of the biological effects of radiation. In 1939, Ernest O. Lawrence won the Nobel Prize for the invention of the cyclotron which was also used in the discovery of plutonium. In 1951, Glenn Seaborg with Edwin M. McMillan won the Nobel Prize for their discoveries in the chemistry of the transuranic elements using the 60-Inch Cyclotron.