The story opens at Dorlcote Mill on the river Floss, where the miller Mr Tulliver lives with his wife and their two children, Tom and Maggie. Tulliver is an honest, hot-headed man, baffled by lawyers and the modern world, who decides to send Tom away for a gentleman's education so the boy can hold his own against sharp men. Maggie, dark, quick, and emotional, is the cleverer of the two, but her intelligence earns more worry than welcome from the comfortable, conventional aunts and uncles of the Dodson family.
Much of the first half is childhood. Maggie adores Tom and lives for his approval, yet she is forever in trouble: cutting off her own hair, forgetting his rabbits, running off briefly to the gypsies. Tom is fair-minded but rigid, and his judgments wound her. At his schooling Maggie also meets Philip Wakem, the gentle, deformed son of the lawyer her father hates, and a friendship begins that will later become dangerous because of the family feud.
The downfall comes when Mr Tulliver loses his ruinous lawsuit, falls ill, and is bankrupted; the mill passes into the hands of his enemy Wakem. The proud Dodson world treats the family as a disgrace. Tom, still young, sets himself grimly to repay every debt and one day recover the mill, while Tulliver, broken and bitter, makes Tom write in the family Bible that he will never forgive Wakem. Maggie, starved of beauty and affection, finds a stern comfort in Thomas a Kempis and a dream of giving herself up entirely.
As a young woman, Maggie meets Philip again in secret in the wooded Red Deeps, and they grow close; but when Tom discovers it, he forces her to break it off, holding her to the family's hatred. Later, on a visit to her cousin Lucy, Maggie is thrown together with Lucy's suitor, the charming Stephen Guest, and a powerful mutual attraction grows between them, though Lucy loves Stephen and Philip loves Maggie. Carried along on a boat trip that drifts far past its limit, Maggie nearly lets the current of feeling decide for her, then refuses to buy her own happiness by betraying Lucy and Philip, and returns alone to face the consequences.
St Ogg's condemns her; even Tom shuts the door against her. Maggie stays near home, isolated and resolved, until a great flood rises on the Floss. She takes a boat out into the danger to reach Tom at the mill, and the two are reunited in the water in a last moment that recalls their childhood. The boat is overwhelmed and brother and sister drown together in an embrace. They are buried under one stone, marked, In their death they were not divided.