Guy Pène du Bois was born in 1884 in Brooklyn. He descended from French immigrants who settled in Louisiana in 1738, and he was raised in a highly cultured household. Dropping out of high school, in 1899, he became the youngest student in William Merritt Chase's school, later known as The New York School of Art. In addition to Chase, he studied with Robert Henri, whose teachings on social realism and following one's own artistic inclinations had great influence. Pène du Bois was greatly impressed with Henri’s credo that “real life” was subject matter for art and, throughout his life, a realist philosophy informed his art as well as his parallel career - art criticism.

In 1905, Pène du Bois went to Paris, where he briefly attended the Académie Colarossi. He began to paint cafe society, a subject that he used over and over. In 1906, because of the death of his father, he returned to the United States and worked as a newspaper music and art critic for a number of prestigious publications. During the ensuing years, his works were rendered in the dark tonalities and impasto associated with the Ashcan School. His mature style was characterized by stylized, rounded, almost sculptural figures painted with invisible brushstrokes. The subjects of his paintings were often members of society whom he gently satirized.

Then, in 1924, when he was in his forties, he spent six years in France, which was a turning point in his painting career away from Henri-influenced New York realism to broader subject matter. After five years of living in France, Pène du Bois was able to observe American life with fresh eyes. His work became more psychologically intense and less satirical.

In 1940, Pène du Bois' autobiography, Artists Say the Silliest Things, was published. In the 1950s, his declining health substantially limited the number of pictures produced, and he died in 1958.

His works can be found in the Crocker Art Museum, Wadsworth Atheneum Museum of Art, Yale University Art Gallery, National Gallery of Art, The Art Institute of Chicago, Museum of Fine Arts, Boston, Detroit Institute of Arts, The Brooklyn Museum of Art, The Metropolitan Museum of Art, Whitney Museum of American Art, Butler Institute of American Art, Pennsylvania Academy of the Fine Arts, Carnegie Museum of Art and many more institutions and collections.