Reginald Marsh was born in Paris on March 14, 1898. As the son of Fred Dana Marsh and Alice Randall Marsh (both noted artists), he pursued drawing from a young age. Once at Yale University, he became a regular illustrator for the Yale Record. Following his graduation in 1920 and a move to New York City, he found work as a freelance illustrator – eventually landing jobs with The Daily News, New Yorker and The Masses. Marsh also began painting once in New York, taking classes from John Sloan at the Art Students League. His teachers included Kenneth Hayes Miller, George Luks, and Jacques Maroger.

Marsh sketched and painted constantly in the pursuit of capturing New York City life. His depictions of the leisure activities in Coney Island, night life in burlesque theaters, rabblerousing on the Bowery and workaday labor at the port of New York, resulted in his close association with the Social Realist movement.

In the mid-1930s Marsh became interested in mural painting. In 1936 he produced two panels for the Federal Building in Washington, D.C. as well as a commission from the Treasury Relief Art Project to paint the panels of the great hall of the Custom House at Bowling Green, New York City. It was during the research phase for these murals that Marsh became deeply interested in the use of photography as studies for his art. Between September and December 1937, he painted the eight small and eight large panels of the Custom House in fresco seco to illustrate the activities of the port of New York, with the small panels showing portraits of great explorers.

Marsh later taught at the Art Students League and was the author of Anatomy for Artists. He received the Gold Medal for Graphic Arts awarded by the American Academy and the National Institute for Arts and Letters shortly before he died from a heart attack on July 3, 1954.