Born in Philadelphia to a tobacco wholesaler, Denslow spent brief periods at the National Academy of Design and the Cooper Union in New York, but was largely self-educated and self-trained.

In the 1880s, he traveled about the United States as an artist and newspaper reporter; he came to Chicago for the World's Columbian Exposition in 1893, and chose to stay.

[3] He also used his copyright to the art of the Baum books to create newspaper comic strips featuring Father Goose and the Scarecrow and Tin Woodman during the first decade of the twentieth century.

The strip, titled Denslow's Scarecrow and [the] Tin Man, was intended to promote a forthcoming sequel he was writing.

His first wife, Annie McCartney (née, Anna M. Lowe, 1856–1908) married him in 1882 and gave birth to his only child, a son, the following year.

[10] Denslow died on March 29, 1915, in the Knickerbocker Hospital, New York City[11] of pneumonia following an alcoholic bender with $250 (equivalent to $7,530 in 2023) obtained from the sale of a cover to Life.