Sherrington, a Londoner by birth, was educated at Cambridge University and St. Thomas's Hospital, London, gaining his BA in natural science in 1883 and his MB in 1885. He then traveled to Europe to study under Rudolf Virchow and Robert Koch in Berlin. After lecturing in physiology at St. Thomas's Hospital, Sherrington was superintendent of the Brown Institute (1891–95), a veterinary hospital of the University of London. He then became professor of physiology, firstly at the University of Liverpool (1895–1913) and then at Oxford University, holding the latter post until his retirement in 1935.

Sherrington's early medical work was in bacteriology. He investigated cholera outbreaks in Spain and Italy and was the first to use diphtheria antitoxin successfully in England, his nephew being the patient. During World War I he tested antitetanus serum on the wounded and also worked (incognito) as a laborer in a munitions factory. He then turned his attention to studies of the reflex actions in man, demonstrating their effect in enabling the nervous system to function as a unit and anticipating Ivan Pavlov in his discovery of the ‘conditioned reflex’. Sherrington also did much work on decerebrate rigidity and the renewal of nerve tissue. For their work on the function of the neuron, Sherrington and Edgar Adrian were jointly awarded the Nobel Prize for physiology or medicine in 1932. Sherrington was knighted in 1922.