Lawrence was the son of a superintendent of public schools in Canton, South Dakota. He was educated at the universities of South Dakota, Minnesota, Chicago, and Yale (where he obtained his PhD in 1925). He taught at Yale before moving in 1928 to the University of California at Berkeley. He was appointed professor there in 1930 and director of the radiation laboratory in 1936.

Lawrence was awarded the 1939 Nobel Prize for physics for his invention of the cyclotron. In the 1920s, experiments on bombardment of nuclei relied on low-energy linear accelerators. Lawrence, in 1930, began experiments to construct a cyclic accelerator. In this device charged particles move in spiral paths under the influence of a vertical magnetic field. The particles move inside two hollow D-shaped metal pieces arranged with a small gap between them. A high-frequency electric field applied between the ‘dees’ gives a ‘kick’ to the particle each time it crosses the gap. By early 1931 the first model (4 inches (10.2 cm) in diameter) produced energies of 13,000 electronvolts.

Subsequently, Lawrence, and other workers, developed larger machines capable of achieving much higher energies for nuclear research. Lawrence also played an important part in the development of the atomic bomb. He was responsible for developing the radiation laboratory (now named for him) into one of the world's leading centers for high-energy physics. Element 103, lawrencium, is named in his honor.