Educated at the National College of San Juan, Alegría acquired a firsthand knowledge of Indian life in his native province of Huamachuco; this first appeared in his novel La serpiente de oro (1935; The Golden Serpent), which portrays the diverse human life to be found along the Marañón River in Peru. Los perros hambrientos (1938; “The Hungry Dogs”) describes the difficulties faced by the sheepherding Indians of the Peruvian highlands. The novel that is generally considered Alegría's masterpiece is El mundo es ancho y ajeno (1941; Broad and Alien is the World ). It depicts in epic manner the struggles of an Indian tribe to survive in the Peruvian highlands against the greed of land-hungry white men. A collection of short fiction (Duelo de caballeros 【1963】) and Novelas completas (1963) were his last works.

In 1930 Alegría joined the militantly pro-Indian Alianza Popular Revolucionaria Americana, whose members were called Apristas, and became an active agitator for social reform. He was twice jailed, in 1931 and 1933, for illegal political activity and was exiled to Chile in 1934. From 1941 to 1948 Alegría lived in the United States, but in 1948 he returned to Peru, where he resided until his death.