Winesburg, Ohio was Sherwood Anderson's breakthrough work, the one that first gained widespread attention for him as an artist, although it was years before he would produce a best seller. He was forty-two when it was published, with two novels published previously that had received little interest from the reading public.

According to the story that Anderson would later relate in his Memoirs, the book started one night when he was living by himself in a run-down rooming house in Chicago, in 1915: it was a place full of would-be artists, and Anderson, who was supporting himself by writing advertising copy, sat down one December evening and, almost miraculously, produced the story "Hands" in one sitting. In the version he often told, the story came out exactly as he wanted it and he never changed a word, although researchers have since turned up drafts that show substantial differences.

Having found his style in this one inspired flash, he went on to develop the other stories that make up Winesburg, Ohio over the next few years. When the book was published in 1919, it did not sell very well, but the critical response marked the author as a man of talent and artistic integrity. Some critics lambasted it for being immoral because of its sexual themes, both hidden and blatant, such as the child molestation charge in "Hands" or the implied impotency in "Respectability."

For each critic put off by the buried subjects, though, there were two or three who appreciated Anderson's courage in examining areas previously untouched by mainstream writers. Anderson's greatest influence on American literature has been indirect, in the ways that Winesburg, Ohio inspired the following generation of post-World War I writers, such as Ernest Hemingway, William Faulkner, Eudora Welty, and John Steinbeck. It was when these writers began speaking of the debt they owed to Sherwood Anderson that the book stopped being just a favorite of writers and gathered mass attention from the public.