Raphael Soyer was born in southern Russia. Both he and his twin brother, Moses, became artists. The family emigrated to the United States in 1912, settling in the Bronx district of New York City.

Raphael Soyer went to the free art schools of Cooper Union between 1914 and 1917 then continuing for two years at the National Academy of Design and later at the Art  Students League.. He was greatly influenced by the Ashcan School artists that described the neighborhoods with which he was familiar.

Soyer became associated with the Fourteenth Street School of painters that included Reginald Marsh, Isabel Bishop, Kenneth Hayes Miller, Peggy Bacon and, his teacher, Guy Pene du Bois. Soyer persistently investigated a number of themes—female nudes, portraits of friends and family, New York and, especially, its people—in his paintings, drawings, watercolors and prints. He also painted a vast number of self-portraits throughout his career. Soyer was adamant in his belief in representational art and strongly opposed the dominant force of abstract art during the late 1940s and early 1950s.

After his time in art school, Soyer did not immediately begin working as a professional artist, and instead painted during his free time while working other jobs. Soyer's first solo exhibition took place in 1929. Beginning in the early 1930s, he showed regularly in the large annual and biennial American exhibitions of the Whitney Museum of American Art, the Carnegie Institute, the Art Institute of Chicago, the Corcoran Gallery of Art, the National Academy of Design, and the Pennsylvania Academy of the Fine Arts. In 1967 the Whitney Museum of American Art exhibited a retrospective of his work.

Museums with his work include the Butler Institute of American Art, the National Gallery of Art, Smithsonian American Art Museum, Metropolitan Museum of Art, Whitney Museum of American Art, Hirshhorn Museum, and others.