Pearl Sydenstricker was raised in Chenchiang in eastern China by her Presbyterian missionary parents. Initially educated by her mother and a Chinese tutor, she was sent at 15 to a boarding school in Shanghai. Two years later she entered Randolph-Macon Woman's College in Lynchburg, Virginia, graduating in 1914 and remaining for a semester as an instructor in psychology.

In May 1917 she married missionary John L. Buck; although later divorced and remarried, she retained the name Buck professionally. She returned to China and taught English literature in Chinese universities in 1925–30. During that time she briefly resumed studying in the United States at Cornell University, where she took her M.A. in 1926. She began contributing articles on Chinese life to American magazines in 1922.

Buck's first published novel, East Wind, West Wind (1930), was written aboard a ship headed for America. The Good Earth (1931), a poignant tale of a Chinese peasant and his slave-wife and their struggle upward, was a best-seller. The book, which won a Pulitzer Prize (1932), established Buck as an interpreter of the East to the West and was adapted for stage and screen. The Good Earth, widely translated, was followed by Sons (1932) and A House Divided (1935); the trilogy was published as The House of Earth (1935). Buck was awarded the Nobel Prize for Literature in 1938. From 1935 Buck lived in the United States. After World War II, in a move to aid illegitimate children of U.S. servicemen in Asian countries, she instituted the Pearl S. Buck Foundation (in 1967 she turned over to the foundation most of her earnings—more than $7,000,000).

Buck turned next to biography with lives of her father, Absalom Sydenstricker, Fighting Angel (1936), and her mother, Caroline, The Exile (1936). Her later novels include Dragon Seed (1942) and Imperial Woman (1956). She also published short stories, such as The First Wife and Other Stories . . . (1933), Far and Near (1947), and The Good Deed (1969); a nonfictional work, The Child Who Never Grew (1950), about her retarded daughter; and three works of autobiography, notably My Several Worlds (1954). She also wrote a number of children's books. Under the name John Sedges she published five novels unlike her others, including a best-seller, The Townsman (1945).