After Göttingen he went to Zurich and then Leyden as a fellow of the Institute of International Education. He then went on to become the assistent professor of theoretical physics at the California Institute of Technology and the University of California in 1929. He subsequently achieved at both institutions associate professor in 1931 and full professor in 1936.

During this time, his work covered numerous areas of physics. Oppenheimer made contributions to cosmic ray theory, quantum mechanics, atomic theory, nuclear physics, fundamental particles, and astrophysics. With the discovery of the neutron in 1932, his work shifted towards this area. In collaboration with Volkov, he showed that given certain conditions a star may gravitationally contract, converting the protons into neutrons, resulting in a neutron star.

During World War II, he was chosen to be the head of the work at Los Almos where the atomic bomb was to be created. He also served as chairman of the General Advisory Committee of the Atomic Energy Commission from 1946-1952. In 1947 he left to become director of the Institute for Advanced Studies at Princeton, until he retired in 1965. In 1948 he was elected President of the American Physical Society, the highest honor physicists can give a colleague. During this time, his research involved the theory of fundamental particles and mesons.