The son of a physics teacher from Frauenfel in Switzerland, Hess was educated at the universities of Lausanne, Bern, Berlin, Kiel, and Zurich where he obtained his MD in 1906. Although he actually began as an ophthalmologist, building up a prosperous practice, he decided in 1912 to abandon it for a career in physiology. After junior posts in Zurich and Bonn he was appointed in 1917 to the directorship of the physiology department at the University of Zurich, where he remained until his retirement in 1951.

In the early 1920s Hess began an important investigation of the interbrain and hypothalamus. To do this he inserted fine electrodes into the brains of cats, and used these to stimulate specific groups of cells. His most startling discovery was that when electrodes in the posterior interbrain were switched on this would instantaneously turn a friendly cat into an aggressive spitting creature – a transformation instantly reversed by a further press of the switch. Other areas found by Hess would induce flight, sleep, or defecation.

Less dramatic perhaps but no less significant were the two main areas identified by Hess in the hypothalamus. Stimulation of the posterior region prepared the animal for action but stimulation of the anterior region tended to cause relaxation. Hess had discovered the control center for the sympathetic and parasympathetic systems.

Hess's work was enormously influential and led to a detailed mapping of the interbrain and hypothalamus by many different workers in various centers over a number of years. For his discovery of “the functional organization of the interbrain” Hess was awarded the 1949 Nobel Prize for physiology or medicine, sharing it with Antonio Egas Moniz.