- A young man who works as a reporter in Winesburg, Ohio. Despite the fact that he is one of the least developed of the major characters, he occupies the central role in the book. As a result of either chance meetings or other people's decisions to confide in him, George is the figure who links many of the novel's disparate stories together.
- A sensitive ex-schoolteacher who was accused of molesting one of his male pupils in a town near Winesburg. His hands are amazingly dexterous, but he has difficulty controlling them, and they tend to wander where they don't belong.
- An aging doctor with a declining practice. He marries a young female patient, but she dies after less than a year. He also develops a close relationship with Elizabeth Willard during her last months.
- George Willard's mother, and Tom Willard's wife. She lives in the family's run-down boarding house, where she is constantly ill and has become an invalid. She displays desperate impotence in her dealings with other people, including her husband and son.
- George Willard's father, a middle-aged man with frustrated political ambitions.
- A doctor who enjoys chatting with George and hinting about a criminal past. He suffers from paranoia, believing that the secret of life is "that everyone in the world is Christ."
- A local girl with whom George Willard has one of his first sexual experiences.
- A wealthy farmer, and a deeply religious man with a brutal, Old Testament sensibility and tendency to terrorize his family.
- Jesse Bentley's daughter. A lonely woman with a vicious temper, she is estranged from her father, and marries young out of a craving for love. Her marriage is not a success.
- Louise Bentley's son and Jesse Bentley's grandson. He goes to live on his grandfather's farm while an adolescent, and ends up terrorized by his grandfather's religious zeal and desire to make contact with God.
- The agent for Standard Oil in Winesburg, he is a man who seizes on strange ideas and talks about them for hours on end. He is compared to a volcano, outwardly calm but always ready to explode with some strange fascination.
- A woman in her twenties who once felt deep love for a man who eventually left Winesburg behind. She is now gradually and unwillingly becoming an old maid.
- The Winesburg telegraph operator. A fat, filthy man, he despises the world--particularly women, whom he calls "bitches."
- A sensitive, deep-thinking young man, and a friend of George Willard.
- A young woman whose first name comes from a drunkard's speech about the perfect woman.
- The successful, popular minister of the Presbyterian Church. He struggles with the sexual temptation of peeping in at Kate Swift's window while he writes his sermons.
- A Winesburg schoolteacher. She sees a "spark of genius" in George Willard and tries to encourage it, but she is also looking for love, and briefly allows him to embrace her in the newspaper office.
- A man from Winesburg who moves to New York and, in the grip of terrible loneliness, becomes slightly unhinged and populates his apartment with imaginary people.
- The daughter of a bookkeeper, she goes on walks with George Willard and even kisses him--mainly, however, to arouse the jealousy of the man she really wants, a local bartender named Handby.
- The son of a store owner. He feels terribly out of place in Winesburg, as if everyone is laughing at him, and is prone to hysterical outbursts. Two of these outbursts are directed at George Willard, who is intrigued by Elmer's personality.
- A married farm hand, about fifty years old, with a good reputation. He works alongside Hal Winters.
- A farm hand who works alongside Ray Pearson, and who has a reputation as a "bad one," for his fights and relationship with women.
- A quiet, likable boy who moves to Winesburg from Cincinnati. He decides to get drunk one night, and finds it a remarkable experience.
- A local girl, who is romantically connected to both Seth Richmond and George Willard.