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 Bevatron was the largest, highest energy accelerator in the world from 1954-1956 and continued to operate until 1993 (joined to the SuperHILAC from 1971-1993, also known as Bevalac). It was used to discover the antiproton and the antineutron and many other subnuclear particles. The Bevatron could accelerate protons to energies of 6.5 GeV and made possible the creation of antiprotons, a discovery that earned Owen Chamberlain and Emilio Segre the Nobel Prize in 1955.