Born in Chicago, Illinois to Lillian (née Warsaw) and Selig Friedman, a sewing machine salesman, Friedman's Jewish parents emigrated to the U.S. from Russia. Jerome Friedman excelled in art but became interested in physics after reading a book on relativity written by Albert Einstein. He turned down a scholarship to the Art Institute of Chicago in order to study physics at the University of Chicago. Whilst there he worked under Enrico Fermi, and eventually received his Ph.D in physics in 1956. In 1960 he joined the physics faculty of the Massachusetts Institute of Technology.
In 1968-69, commuting between MIT and California, he conducted experiments with Henry W. Kendall and Richard E. Taylor at the Stanford Linear Accelerator Center which gave the first experimental evidence that protons had an internal structure, later known to be quarks. For this, Friedman, Kendall and Taylor shared the 1990 Nobel Prize in Physics. He is an Institute Professor at the Massachusetts Institute of Technology. Friedman is also a member of the Board of Sponsors of the Bulletin of the Atomic Scientists.
In 2003 he was one of 22 Nobel Laureates who signed the Humanist Manifesto. He is an atheist.
In 2008, Friedman received an honorary Ph.D from the University of Belgrade. He is an honorary professor at the University of Belgrade's Faculty of Physics and the Faculty's world-famous institutes: Institute of Physics, Institute of Physics, Zemun and Vinca Nuclear Institute.