Derain was born in 1880 in Chatou, Yvelines, Île-de-France, just outside Paris. In 1895 Derain began to study on his own, contrary to claims that meeting Vlaminck or Matisse began his efforts to paint, and occasionally went to the countryside with an old friend of Cézanne's, Father Jacomin along with his two sons. In 1898, while studying to be an engineer at the Académie Camillo, he attended painting classes under Eugène Carrière, and there met Matisse. In 1900, he met and shared a studio with Maurice de Vlaminck and together they began to paint scenes in the neighbourhood, but this was interrupted by military service at Commercy from September 1901 to 1904. Following his release from service, Derain attended the Académie Julian.
At about this time Derain's work began overtly reflecting his study of the Old Masters. In 1910, however, Derain destroyed much of his unsold work. Yet soon after this artistic crisis, Derain returned to his study of landscape painting, while also making vanitas still lifes in a proto-Cubist style. Late Gothic and early Renaissance themes feature in paintings such the pseudo-religious Saturday (Le Samedi, 1913), while works such as Italian Woman (L’Italienne, 1913) demonstrate an increasingly stark and geometric classicism. The role of color was reduced and forms became austere; the years 1911–1914 are sometimes referred to as his gothic period. In 1914 he was mobilized for military service in World War I and until his release in 1919 he would have little time for painting, although in 1916 he provided a set of illustrations for André Breton's first book, Mont de Piete.
After the war, Derain won new acclaim as a leader of the renewed classicism then ascendant. With the wildness of his Fauve years far behind, he was admired as an upholder of tradition. In 1919 he designed the ballet La Boutique fantasque for Diaghilev, leader of the Ballets Russes. A major success, it would lead to his creating many ballet designs.
The 1920s marked the height of his success, as he was awarded the Carnegie Prize in 1928 for his "Still-life with Dead Game" and began to exhibit extensively abroad—in London, Berlin, Frankfurt, Düsseldorf, New York City and Cincinnati, Ohio. In the 1920s he worked on a series of nudes and other figurative works such as Harlequin and Pierrot (Arlequin et Pierrot, ca. 1924). Classical mythology appears in his work from the 1930s on, as in Return of Ulysses (Le retour d’Ulysse, 1938), which combines Last Supper imagery with that of a Homeric banquet.
After the end of World War II, Derain made a number of landscapes of Normandy (in 1949), as well as illustrations and metal sculptures. He died on September 9, 1954, in Paris.