The novel spans a period of 10 to 15 years and details the lives of Tom and Maggie Tulliver, siblings growing up at Dorlcote Mill on the River Floss at its junction with the more minor River Ripple near the village of St. Ogg's in Lincolnshire, England. Both the river and the village are fictional.
The novel is most probably set in the 1820s – a number of historical references place the events in the book after the Napoleonic Wars but before the Reform Act of 1832. It includes autobiographical elements, and reflects the disgrace that George Eliot (Mary Ann Evans) herself experienced while in a lengthy relationship with a married man, George Henry Lewes.
Maggie Tulliver is the central character of the book. The story begins when she is 9 years old, 13 years into her parents' marriage. Her relationship with her older brother Tom, and her romantic relationships with Philip Wakem, a hunchbacked, sensitive, and intellectual friend, and with Stephen Guest, a vivacious young socialite in St. Ogg's and assumed fiancé of Maggie's cousin Lucy Deane, constitute the most significant narrative threads.
Tom and Maggie have a close yet complex bond, which continues throughout the novel. Their relationship is coloured by Maggie's desire to recapture the unconditional love her father provides before his death. Tom's pragmatic and reserved nature clashes with Maggie's idealism and fervor for intellectual gains and experience. Various family crises, including bankruptcy, Mr. Tulliver's rancorous relationship with Philip Wakem's father, which results in the loss of the mill, and Mr. Tulliver's untimely death, serve both to intensify Tom's and Maggie's differences and to highlight their love for each other. To help his father repay his debts, Tom leaves school to enter a life of business. He eventually finds a measure of success, restoring the family's former estate. Meanwhile, Maggie languishes in the impoverished Tulliver home, her intellectual aptitude wasted in her socially isolated state. She passes through a period of intense spirituality, during which she renounces the world, spurred by Thomas à Kempis’s The Imitation of Christ.
This renunciation is tested by a renewed friendship with Philip Wakem, with whom she had developed a friendship while he and Tom were students together. Against the wishes of Tom and her father, who both despise the Wakems, Maggie secretly meets with Philip, and together they go for long walks through the woods. The relationship they forge is founded partially in Maggie's heartfelt pity for broken and neglected human beings, but it also serves as an outlet for her intellectual romantic desires. Philip's and Maggie's attraction is, in any case, inconsequential because of the family antipathy. Philip manages to coax a pledge of love from Maggie. When Tom discovers the relationship between the two, however, he forces his sister to renounce Philip, and with him her hopes of experiencing the broader, more cultured world he represents.
Several more years pass, during which Mr. Tulliver dies. Lucy Deane invites Maggie to come and stay with her and experience the life of cultured leisure that she enjoys. This includes long hours conversing and playing music with Lucy's suitor, Stephen Guest, a prominent St. Ogg's resident. Stephen and Maggie, against their rational judgments, become attracted to each other. The complication is compounded by Philip Wakem's friendship with Lucy and Stephen; he and Maggie are reintroduced, and Philip's love for her is rekindled, while Maggie, no longer isolated, enjoys the clandestine attentions of Stephen Guest, putting her past profession of love for Philip in question. Lucy intrigues to throw Philip and Maggie together on a short rowing trip down the Floss, but Stephen unwittingly takes a sick Philip's place. When Maggie and Stephen find themselves floating down the river, negligent of the distance they have covered, he proposes they board a passing boat to the next substantial city, Mudport, and get married. Maggie is too tired to argue about it. Stephen takes advantage of her weariness and hails the boat. They are taken on board the boat, and during the trip to Mudport, Maggie struggles between her love for Stephen and her duties to Philip and Lucy, which were established when she was poor, isolated, and dependent on them for what good her life contained. Upon arrival in Mudport she rejects Stephen and makes her way back to St. Ogg's, where she lives for a brief period as an outcast, Stephen having fled to Holland. Although she immediately goes to Tom for forgiveness and shelter, he roughly sends her away, telling her that she will never again be welcome under his roof. Both Lucy and Philip forgive her, in a moving reunion and an eloquent letter, respectively.
Maggie’s brief exile ends when the river floods. The flood has been criticised as a deus ex machina. Those who do not support this view cite the frequent references to flood as foreshadowing, which makes this natural occurrence less contrived. Having struggled through the waters in a boat to find Tom at the old mill, she sets out with him to rescue Lucy Deane and her family. In a brief tender moment, the brother and sister are reconciled from all past differences. When their boat capsizes, the two drown in an embrace, thus giving the book its Biblical epigraph, "In their death they were not divided."
- Maggie Tulliver – young female protagonist
- Tom Tulliver – Maggie's brother
- Mrs Bessy Tulliver – Maggie and Tom's mother
- Mr Tulliver – Maggie and Tom's father, owner of the Mill
- Philip Wakem – hunchbacked classmate of Tom, and friend/suitor to Maggie
- Stephen Guest – affluent suitor to Maggie
- Mr. Wakem – Philip's father and rival of Mr Tulliver
- Lucy Deane – Tom and Maggie's cousin, supposed to be betrothed to Stephen Guest
- Mr. Riley – auctioneer and appraiser, friend of Mr. Tulliver
- Rev. Walter Stelling – teacher of Tom and Phillip
- Dr. Kenn – the clergyman of St. Ogg's
- Bob Jakin – childhood friend of Tom who later helps Tom in business, both Tom and Maggie stay at his house at different times
- Mrs. Jane Glegg – leader of the Dodson clan, critical and dominating aunt of Maggie and Tom who stands up for Maggie after her scandal with Stephen
- Mrs. Sophy Pullet – Tom and Maggie's aunt
- Mrs. Susan Deane – Tom and Maggie's aunt
- Gritty Moss – Mr Tulliver's sister, mother of 8 children, 6 living
- Kezia – The Tulliver family maid
- Luke – the head miller
- Yap – the Tullivers' dog (white and brown)
- Dr. Turnbull - Doctor of Dorlecote Mill
- Dorlecote Mill – the Tulliver family home for a century
- Basset – home of Moss Farm
- Dunlow Common
- Garum Firs – visited for a treat
- Midsummer – home of the academy
- St. Ogg's
- St. Ursula