Schwinger, who was born in New York City, developed his prowess for mathematics and physics at an early age. At 14 he entered the City College of New York, but later transferred to Columbia University. He received his BA degree from Columbia at the age of 17 (1936) and his doctorate three years later. Moving to the University of California at Berkeley, he worked as a research associate under J. Robert Oppenheimer. In the war years (1943–45) he worked at the Metallurgical Laboratory of the University of Chicago and at the Radiation Laboratory of the Massachusetts Institute of Technology. In 1945 he joined the faculty of Harvard as an associate professor of physics, and the next year was made full professor, one of the youngest in Harvard's history. He became professor of physics at the University of California, Los Angeles, in 1972.

Schwinger's most notable contribution to physics was in the fusion of electromagnetic theory and quantum mechanics into the science of quantum electrodynamics (the foundations of which had been laid by Paul Dirac, Werner Heisenberg, and Wolfgang Pauli). During World War II, Schwinger, and others such as Richard Feynman, Sin-Itiro Tomonaga, and Frank Dyson, developed the mathematical formulation of quantum electrodynamics in a way that was consistent with Einstein's theory of relativity. The new theory led to a better understanding of the interactions between charged particles and electromagnetic fields and proved useful in measuring and explaining the behavior of atomic and subatomic particles. Schwinger, Feynman, and Tomonaga, who had conducted their work independently – Feynman at the California Institute of Technology and Tomonaga at the Tokyo Education University – were subsequently rewarded with the 1965 Nobel Prize for physics.

Schwinger also conducted significant research into the properties of synchrotron radiation, produced when a fast moving charged particle is diverted in a magnetic field. He was the author of Particles Sources and Fields (1970).