Sperry, who was born in Hartford, Connecticut, studied psychology at Oberlin College and zoology at the University of Chicago, where he obtained his PhD in 1941. He worked at Harvard, the Yerkes Primate Center, and at Chicago before he moved to the California Institute of Technology in 1954 as professor of psychobiology where he remained until 1984.

Sperry worked on the hemispheres of the brain. Architecturally the brain consists of two apparently identical halves constructed in such a way that each half controls the opposite side of the body. The language center of the human brain is located in most people in the left side alone. The two cerebral hemispheres are far from distinct anatomically, with a number of bands of nervous tissue (commissures) carrying many fibers from one side to the other. In the early 1950s Sperry set out to find how a creature would behave if all such commissures were severed resulting in a ‘split brain’. To his surprise he found that monkeys and cats with split brains act much the same as normal animals. However, where learning was involved the creatures behaved as if they had two independent brains. Thus if a monkey was trained to discriminate between a square and a circle with one eye, the other being covered with a patch, then, if the situation was reversed the animal would have to relearn how to make the discrimination.

He also studied a 49-year-old man whose brain had been ‘split’ to prevent the spread of severe epileptic convulsions from one side to the other. He found that, though normal in other ways, the patient showed the effect of cerebral disconnection in any situation that required judgment or interpretation based on language. Sperry's work immediately posed the problem of whether there is any comparable specialization inherent in the human right-hand brain. This topic is receiving much attention.

Sperry also performed some equally dramatic experiments on nerve regeneration in amphibians. Although in mammals a severed optic nerve remains permanently severed, in certain amphibians such as the salamander it will regenerate. Sperry wondered if the nerves regenerate along the old pathway or whether a new one is formed. He found that whatever obstacles were placed before the nerve fiber it would invariably, however tortuous the path might be, find its way back to its original synaptic connection in the brain. This was shown most convincingly when, after severing the optic nerve, Sperry removed the eye, rotated it through 180° and replaced it. When food was presented to the right of the animal it would aim to the left, thus clearly showing the fibers had made their old functional connection. Sperry shared the 1981 Nobel Prize for physiology or medicine with David Hubel and Torsten Wiesel.