Ramón J. Sender was born in Chalamera, Huesca Province in the autonomous region of Aragon in Spain. In 1923 he was obliged to serve in the Spanish military and take part in the Spain Morocco Rif War, which lasted from 1919 to 1926. Later that year he returned to Madrid, where he worked as a journalist for El Sol, a paper critical of the current government. In 1926 he was imprisoned for writing Casas viejas. When the Spanish Civil War began in 1936, Sender immediately enlisted to help resist Franco. While he was at the front, the Nationalists shot his wife, Amparo Barayon, in Zamora and his brother in Huesca. He had been an anarchist and then a communist but after the Spanish Civil War he reneged of this ideology and sought asylum in France in 1938. He left Spain for New York after the Spanish Civil War in 1939, and then relocated to Mexico like many scientists, artists and intellectuals during the government of Lázaro Cárdenas. He became an American citizen in 1948, and he lived in the United States until 1972, when he returned to live in Spain for several years before dying in San Diego, California in 1982. Sender's son is composer and writer Ramon Sender. His grandson is Chicago-based designer Sol Sender, best known for the development of Obama campaign logo.

His most famous works include La tesis de Nancy, about the experiences of a young American student in Spain named Nancy, and Réquiem por un campesino español. La tesis de Nancy is widely read by Spanish students. The book is a true account based upon a series of letters written by Nancy (originally in English) from Nancy to her aunt. At the time Nancy was studying and living in Spain. She shared with her aunt her love for learning and exploring the Spanish language.