Chicago-born Friedman was educated at the university in his native city and gained his PhD there in 1956. After spending three years in California at Stanford, Friedman moved to the Massachusetts Institute of Technology in 1961, and was later appointed to a chair of physics in 1967.

Working with his MIT colleague Henry Kendall (1926–1999) and with Richard Taylor (1929–2018) from Stanford, Friedman began to study the internal structure of the proton. They worked with the 3-kilometer linear accelerator recently opened at Stanford (SLAC). Electrons were accelerated to an energy of 20,000 million electronvolts and directed against a target of liquid hydrogen. In a manner reminiscent of the 1911 experiments of Ernest Rutherford, they analyzed the angles and energies of the electrons and protons of the hydrogen nuclei as they scattered after collision. Similar experiments had been performed by Robert Hofstadter in the 1950s and he had found protons not to be mere points, but fuzzy blobs spread out over an area of about 10^–15 meter. In 1967, however, higher energies were available to Friedman and his colleagues, which led them to hope that they might see into the proton with a little more precision.

In cases of elastic scattering, where beam and target particles retain their identity, the deflections were minor and occurred as expected. When, however, the scattering was inelastic and the protons were struck with sufficient energy to produce new particles, such as pions, the electrons were deflected through much wider angles than expected.

These latter scattering results proved difficult to explain. A possible answer was proposed by Richard Feynmann in 1968 on a visit to SLAC. Protons, he suggested, could be composed of a number of pointlike particles, which he called “partons.” From such charged points, electrons could be scattered through large angles. Further, it followed from the angular distribution of the scattered electrons that the partons must have a spin of one half.

As these were the properties calculated for the hypothetical quarks proposed by Murray Gell-Mann, the SLAC experiment was soon taken to be the first experimental evidence for the existence of quarks. It was for this work that Friedman shared the 1990 Nobel Prize for physics with his collaborators Kendall and Taylor.