Du Bois was born in Brooklyn, New York. From 1899 to 1905 he attended the New York School of Art and the Art Students League where his teachers were William Merritt Chase, Robert Henri and Kenneth Hayes Miller. In late 1905 Du Bois went to Paris for a year and studied with Theophile Steinlen. After returning to America he pursued a second career as an art critic, and in the ensuing years he worked on the staff of the New York American, New York Tribune, Arts Weekly, and New York Evening Post, contributed articles to such magazines as Creative Art, The Arts and The New Yorker, served as editor of Arts and Decoration, and wrote monographs on John Sloan, William Glackens, Edward Hopper and Ernest Lawson. His autobiography Artists Say the Silliest Things was published in 1940.

From 1923 until his death in 1958, Pène du Bois lived on or close to New York's Washington Square Park. He had a studio at 3 Washington Square South from 1933 to 1938 and again in the early 1950s. Chess Tables Washington Square dates from about 1950 and is the only easel painting Pène du Bois is known to have painted of the Square. The work relates to a group of drawings he created of people milling about the chess tables at the southeast corner of the park. Some of the drawings were made from a window of the Holley Hotel at 32 Washington Square West. Beginning in the 1940s, the artist's works became dreamier, moodier, and more evocative. Pène du Bois authority Betsy Fahlman has noted that now "forms were no longer materialized and color [was] less solid…more loosely brushed [and] suffused with a mysterious light" ("Guy Pène du Bois: Painter, Critic, Teacher," Ph.D. dissertation, University of Delaware, 1981, p. 171).