The Mill on the Floss, published in 1860, is based partially on Eliot's own experiences with her family and her brother Isaac, who was three years older than Eliot. Eliot's father, like Mr. Tulliver in the novel, was a businessman who had married a woman from a higher social class, whose sisters were rich, ultra-respectable, and self-satisfied; these maternal aunts provided the character models for the aunts in the novel. Like Maggie, Eliot was disorderly and energetic and did not fit traditional models of feminine beauty or behavior, causing her family a great deal of consternation.

By the time Eliot published The Mill on the Floss, she had gained considerable notoriety as an "immoral woman" because she was living with the writer George Henry Lewes, who was married, though separated from his wife. Social disapproval of her actions spilled over into commentary on the novel, and it was scathingly criticized because it did not present a clear drama of right and wrong. Perhaps the most offended reader was Eliot's brother Isaac, who was very close to her in childhood but who had become estranged from her when he found out about her life with Lewes; he communicated with her only through his lawyer. In the book, Eliot drew on her own experiences with a once-beloved but rigid and controlling brother to depict the relationship between Maggie and her brother Tom.