Szent-Györgyi, who was born in the Hungarian capital Budapest, studied anatomy at the university there, obtaining his MD in 1917. He continued his studies in Hamburg, Groningen, and at Cambridge University where he received his PhD in 1927. He also spent some time at the Mayo Clinic, Minnesota, before returning to Hungary as professor of medical chemistry at the University of Szeged. In 1947, however, he emigrated to America becoming director of the Institute for Muscle Research at the Marine Biological Station, Woods Hole, Massachusetts.

Szent-Györgyi, a highly original and productive biochemist, first became widely known in the late 1920s for his work on the adrenal glands. In the usually fatal condition Addison's disease, where the adrenal glands cease to function, one symptom is a brown pigmentation of the skin. Szent-Györgyi wondered if there was a connection between this and the browning of certain bruised fruits, which is due to the oxidation of phenolics to quinole. Some fruits, notably citrus, do not go brown because they contain a substance that inhibits this reaction. Szent-Györgyi isolated a substance from adrenal glands, which he named hexuronic acid, that also turned out to be present in nonbruising citrus fruits known for their high vitamin C content. He suspected he had finally succeeded in isolating the elusive vitamin but was anticipated in announcing his discovery by Charles King, who published his own results two weeks earlier. The main reason for Szent-Györgyi's delay was the problem of supply. However when he began work in Szeged, with its paprika milling industry, he found a rich supply of the vitamin in Hungarian paprika and was soon able to confirm his suppositions and further investigate the action of the vitamin in the body.

Szent-Györgyi also studied the uptake of oxygen in isolated muscle tissue and found that he could maintain the rate of uptake by adding any one of the four acids – succinic, fumaric, malic, or oxaloacetic. This work was extended by Hans Krebs and led to the elucidation of the Krebs cycle. For his studies into “biological combustion processes” Szent-Györgyi was awarded the 1937 Nobel Prize for physiology or medicine.

In addition to such work Szent-Györgyi became widely known for his studies into the biochemistry of muscular contraction. It was known that the contractile part of muscle was made mainly from the two proteins, actin and myosin. In 1942, in collaboration with Ferenc Straub, Szent-Györgyi showed that the two proteins can be encouraged to form fibers of actomyosin which, in the presence of ATP, the cell's energy source, will contract spontaneously. Just how the combining of the two proteins can lead to muscular contraction was a question pursued and illuminated by Hugh Huxley.