Vitamin C is a vitamin for only a limited number of vertebrate species: humans and the other primates, the guinea pig, bats, the passeriform birds, and most fishes. Most insects and invertebrates are also incapable of ascorbate synthesis. Ascorbate is synthesized as an intermediate in the gulonolactone pathway of glucose metabolism; in those vertebrate species for which ascorbate is a vitamin, one enzyme of the pathway, gulonolactone oxidase, is absent.

The vitamin C deficiency disease, scurvy, has been known for many centuries, and was described in the Ebers papyrus of 1500 B.C. and by Hippocrates. The Crusaders are said to have lost more men through scurvy than were killed in battle; in some of the long voyages of exploration of the fourteenth and fifteenth centuries, upto 90% of the crew died from scurvy. Cartier's expedition to Quebec in 1535 was struck by scurvy; the local native Americans taught him to use infusion of swamp spruce leaves to prevent or cure the condition. Recognition that scurvy was the result of a dietary deficiency came relatively early. James Lind demonstrated in 1757 that orange and lemon juice were protective, and Cook maintained his crew in good health during his circumnavigation of the globe (1772 to 1775) by stopping frequently to take on fresh fruit and vegetables. In 1804, the British Navy decreed a daily ration of lemon or lime juice for all ratings, a requirement that was extended to the merchant navy in 1865.

Ascorbic acid was isolated from cabbage, lemon juice, and adrenal glands by Szent-György in 1928, and identified as the antiscorbutic factor by Waugh and King in 1932. Its structure was established by Haworth and coworkers in 1933, and the same year Haworth, in Birmingham, and Reichstein, in Switzerland, succeeded in synthesizing the vitamin.