The Mill on the Floss opens with the unnamed narrator dreaming of Dorlcote Mill as she or he knew it years ago. At that time, Mr. Tulliver, owner of the mill and its farm, has decided to send his son, Tom, away to school so that he can become something more than a miller and farmer. When Tom gets home for the summer, he learns that his younger sister Maggie forgot to feed his rabbits and they have all died, so he is furious with her. Maggie is a very bright girl with good intentions and a strong desire to please her brother, so this devastates her. As will happen frequently throughout their lives, Tom coldly holds her carelessness against her for a little while before forgiving her.
Tom's schooling at Mr. Stelling’s begins. Tom finds the lessons largely unpleasant, as he is the only pupil and it is the kind of learning that he finds the most difficult. After the Christmas holiday, though, Philip Wakem joins him at King's Lorton to learn from Mr. Stelling. Philip is the son of Mr. Wakem, a lawyer whom Mr. Tulliver detests, so Tom is prepared to dislike him. Tom is also disturbed by Philip’s physical deformity. Philip is overly sensitive but an apt pupil, so he also has a problem with the brutish miller's son. The two reach a wary peace, however, especially when Maggie comes to visit, as Philip is greatly impressed with her intelligence and kind nature.
Two years later, Maggie goes away to school with her cousin Lucy, but is called home when Mr. Tulliver has lost his lawsuit against Mr. Pivart, a neighboring farmer represented by Mr. Wakem. The loss of the suit combined with his legal fees means he will lose the mill and be completely bankrupt. Right before Maggie’s return, he learns that the mortgage on the farm has fallen into Mr. Wakem’s hands, and this news on top of everything else causes him to lose his senses. Maggie goes to Mr. Stelling’s to deliver the news to Tom, who comes home with her.
There they find that Mr. Tulliver recognizes only Maggie, and a bailiff has come to sell off all of their household goods and furniture, which Mr. Tulliver had used as a security against one of his loans. Mrs. Tulliver turns to her sisters - Mrs. Pullet, Deane and Glegg - for help, but they are more interested in making their moral superiority known, and they only buy the goods that they would want anyway. Tom goes to his uncle Deane for advice on starting out in business so that he can help his family. Mr. Deane is somewhat discouraging, but he eventually finds Tom a starting position at Guest & Co., Mr. Deane's employer, and sets him up with lessons in bookkeeping.
Mrs. Tulliver goes to see Mr. Wakem to try to discourage him from buying the mill when it comes up at auction, but she inadvertently convinces him to do just that. Mr. Tulliver has been slowly improving, and when they tell him that Mr. Wakem now owns the mill and is willing to keep him on as manager, he agrees to do so even though he despises the idea of working under Mr. Wakem, since he believes he owes it to his wife, and he doesn’t want to make his family have to move.
Mr. Tulliver’s only focus now is on saving enough money to repay all of his remaining outstanding debts. Tom and Mrs. Tulliver agree this is the honorable thing to do, so Tom gives all of his earnings from his new job to this cause, and Mrs. Tulliver does everything she can to economize. Bob Jakin gives Maggie a pile of books as a gift, among which is a spiritual treatise which recommends self-renunciation as the path to peace. Maggie becomes convinced this is the only way she will be happy, but she goes at it with an egotistical zeal which is against the true nature of the renunciation.
Bob Jakin offers Tom (now 19) an investment opportunity that he takes with the help of Mr. and Mrs. Glegg, and he manages to quickly multiply his savings. Meanwhile, Philip Wakem meets Maggie on one of her walks, and pleads with her to meet with him regularly, secretly. She eventually agrees, and they do so for almost a year. Philip finally tells Maggie that he is in love with her, and she tells him that she can’t imagine loving anyone more than she does him, but she could never marry him and risk hurting her father and brother so deeply.
Tom figures out that Maggie has been meeting Philip and tells her that if she ever sees or communicates with Philip again without Tom’s permission, he will tell their father all about it, which will probably cause him to lose his sanity again. She accepts his terms, and Tom follows her to her next meeting with Philip. Tom is very cruel to him, and Maggie tells Philip she must end their friendship.
Tom manages to earn enough money with his investments to pay back all of Mr. Tulliver’s debt. Mr. Tulliver is joyous, and decides to quit working for Mr. Wakem, but when he runs into him and tells him this, his anger gets the best of him and he ends up attacking Mr. Wakem with a horsewhip. This brings on a stroke of some sort for Mr. Tulliver, and he dies soon after, telling Tom that he should work to buy the mill back, and he should never forgive the Wakems.
Two years later, Maggie returns to St. Ogg’s to stay with her cousin Lucy Deane after having worked at a school since her father’s death. When Maggie learns of Lucy's friendship with Philip Wakem, she tells Lucy about her prior, forbidden relationship with him; Lucy begins to scheme ways to get the pair together. Maggie meets Stephen Guest, who has been courting Lucy, and immediately is very attracted to him, and he to her. Though they both try to ignore their feelings, eventually they are overwhelmed by them, and so Maggie goes to visit her aunt Moss to get away for a little. Stephen comes to her there and tells her that he loves her and that they have to be together. Though Maggie is tempted, she insists that she could never be happy with him because of the guilt she would feel about Lucy and Philip.
When Maggie returns to St. Ogg’s, Lucy, trying to solidify the relationship between Maggie and Philip, arranges for them to be alone on a boat ride. Philip, though, is depressed because he has realized Maggie and Stephen have feelings for one another, so he arranges to have Stephen take his place, unintentionally leading to Stephen and Maggie being alone in the boat together. Stephen convinces Maggie to elope with him, so they leave the rowboat for a steamship to York. The next morning, however, when they dock, Maggie realizes she can’t allow herself to get her happiness out of Philip and Lucy’s hurt, so she tells Stephen she can’t marry him after all, and heads back to St. Ogg’s.
When Maggie returns to St. Ogg’s five days later, everyone believes the worst of her, including Tom, who refuses to offer her a home with him. Mrs. Tulliver supports her, though, and together they lodge at childhood friend Bob Jakin’s. A letter comes from Stephen to his father, absolving Maggie of guilt, but the damage to her reputation has been done. The town’s clergyman, Dr. Kenn, tries to help her and even gives her a job as governess to his children, but when rumors start to swirl about the two of them, he tells her it would be best if she moved to another town altogether.
Lucy, who has been unwell since the shock of Maggie and Stephen running off together, sneaks out one night to visit Maggie and tells her that once she is well again, she will come see her often. Maggie gets two letters, one from Philip telling her he doesn’t blame her and wishes her to feel no guilt for his sake, and one from Stephen pleading with her to marry him. She resolves to turn him down for good.
She realizes the house is flooding and, after waking Bob and his family, gets into a boat to get to Dorlcote Mill. Mrs. Tulliver is safely out of town, but Tom is there and gets into the boat with her. They have a moment of unspoken resolution, but a large piece of debris comes right into their path and drowns them. Everyone else survives the flood and the siblings are buried next to one another.