The book is written as a series of letters from Frances "Fanny" Hill to an unknown woman, with Fanny justifying her life-choices to this individual. At the beginning of her tale, Fanny Hill is a young girl with a rudimentary education living in a small village near Liverpool. Shortly after she turns 15, both her parents die. Esther Davis, a girl from Fanny's village who has since moved to London, convinces Fanny to move to the city as well, but Esther abandons Fanny once they arrive. Fanny hopes to find work as a maid, and is hired by Mrs. Brown, a woman she believes to be a wealthy lady. Mrs. Brown is in fact a madam (pimp) and intends the innocent Fanny to work for her as a prostitute. Mrs. Brown's associate, Phoebe Ayers, shares a bed with Fanny and introduces her to sexual pleasure while establishing that her hymen is intact. Mrs. Brown plans to sell Fanny's virginity to an ugly old man, but Fanny is repulsed by the man and struggles with him. She is saved from rape by Mrs. Brown's maid. After this ordeal, Fanny falls into a fever for several days. Mrs. Brown, realizing that Fanny's virginity is still intact, decides to sell Fanny's sexual favors to the exceedingly rich Lord B., who is due to arrive in a few weeks.
Fanny spies on Mrs. Brown having sex with a large, muscular man. Fanny masturbates while watching them, but is also frightened by the size of the man's penis. She talks to Phoebe, who assures her that it is possible for a young girl to have sex with a well-endowed man. She takes Fanny to spy on another prostitute, Polly Phillips, having sex with a handsome and well-endowed young Genoese merchant. Afterward, Phoebe and Fanny engage in mutual masturbation and Fanny looks forward to her first time having sex with a man.
Soon afterward, Fanny meets Charles, a 19-year-old wealthy nobleman, and they fall in love instantly. Charles helps Fanny escape the brothel the next day. They go to an inn outside London, where Fanny has sex with Charles for several days. Charles takes Fanny to his flat at St. James's, London, and introduces her to his landlady, Mrs. Jones. For many months, Charles visits Fanny almost daily to have sex. Fanny works hard to become more educated and urbane. After eight months, Fanny becomes pregnant. Three months later, Charles mysteriously disappears. Mrs. Jones learns that Charles' father has kidnapped Charles and sent him to the South Seas to win a fortune. Upset by the news that Charles will be gone for at least three years, Fanny miscarries and falls ill. She is nursed back to health by Mrs. Jones, but sinks into a deep depression.
Mrs. Jones tells Fanny that the now-16-year-old girl must work as a prostitute for her. Mrs. Jones introduces Fanny to Mr. H, a tall, rich, muscular, hairy-chested man. Fanny unwittingly drinks an aphrodisiac, and has sex with Mr. H. She concludes that sex can be had for pleasure, not just love. Mr. H puts Fanny up in a new apartment and begins paying her with jewels, clothes, and art. After seven months, Fanny discovers that Mr. H has been having sex with her maid, so she resolves to seduce Will, Mr. H's 19-year-old servant. Will has an extremely large penis: "not the plaything of a boy, nor the weapon of a man, but a Maypole, of so enormous a standard, that, had proportions been observed, it must have belonged to a young giant...In short, it stood an object of terror and delight". A month later, Mr. H catches Fanny having sex with Will, and stops supporting her.
Fanny is taken in by Mrs. Cole, the mistress of one of Mr. H's friends, who also happens to run a brothel in the Covent Garden neighborhood of London. Fanny meets three other prostitutes, who are also living in the house:
- Emily, a blonde girl in her early 20s who ran away at the age of 14 from her country home to London. She met a 15-year-old boy who, being sexually experienced, engaged in sexual intercourse with virgin Emily. Although the two lived together a short time, Emily became a street prostitute for several years before being taken in by Mrs. Cole.
- Harriet, a brunette and an orphan raised by her aunt, had her first sexual experience with the son of Lord N., a nobleman whose estate adjoined her relative's.
- Louisa, the bastard daughter of a cabinetmaker and a maid who entered puberty at a very young age and began engaging in extensive masturbation. While visiting her mother in London, Louisa began masturbating in her mother's bedroom. The landlady's 19-year-old son caught her and made love to the 13-year-old girl. Louisa spent the next few years having sex with as many men as she could and turned to prostitution as a means of satisfying her lust.
A short time later, Fanny participates in an orgy with the three girls and four rich noblemen. Fanny and her young nobleman begin a relationship, but it ends after a few months because the young man moves to Ireland. Mrs. Cole next introduces Fanny to Mr. Norbert, an impotent alcoholic and drug addict who engages in rape fantasies with prostitutes. Unhappy with Mr. Norbert's impotence, Fanny engages in anonymous sex with a sailor in the Royal Navy. However, Mr. Norbert soon dies. Mrs. Cole then introduces Fanny to Mr. Barville, a rich, young masochist who requires whipping to enjoy sex. After a short affair, Fanny begins a sexual relationship with an elderly customer who becomes sexually aroused by caressing her hair and biting the fingertips off her gloves. After this ends, Fanny enters a period of celibacy.
Emily and Louisa go to a drag ball, where Emily meets a bisexual young man who believes Emily is a male. When he finds out that she is actually a female, he has sex with Emily in his carriage. Fanny is confused by her first encounter with male homosexuality. Shortly after this incident, Fanny takes a ride in the country and ends up paying for a room at a public tavern after her carriage breaks down. She spies on two young men engaging in anal sex in the next room. Startled, she falls off a stool and knocks herself unconscious. Although the two men have left, she still rouses the villagers to try to hunt the two men down and punish them.
Some weeks later, Fanny watches as Louisa seduces the teenage son of a local woman. Fanny believes that the boy's erect penis is even larger than Will's. The boy, clearly a virgin, engages in somewhat violent, brutal sex several times with Louisa. Louisa leaves Mrs. Cole's brothel a short time later after falling in love with another young man. Emily and Fanny are then invited by two gentleman to a country estate. They swim in a stream, and the two men have sex with the girls for several hours. Emily's parents soon find their daughter, and (unaware of her career as a prostitute) ask her to come home again. She accepts.
Mrs. Cole retires, and Fanny starts living off her savings. One day she encounters a man of 60 who looks 45 due to his lifestyle: "He was, as I afterwards learn'd in the course of the intimacy which this little accident gave birth to, an old bachelor, turn'd of sixty, but of a fresh vigorous complexion, insomuch that he scarce marked five and forty, having never rack'd his constitution by permitting his desires to overtax his ability." The man falls in love with Fanny but treats her like his daughter. He dies and leaves his small fortune to her. Now 18 years old, Fanny uses her new wealth to try to locate Charles. She learns that he disappeared two and a half years ago after reaching the South Seas. Several months later, a despondent Fanny takes a trip to see Mrs. Cole (who had retired to Liverpool), but a storm forces her to stop at an inn along the way, where she runs into Charles: He had come back to England but was shipwrecked on the Irish coast. Fanny and Charles get a room together and make love several times. Fanny tells Charles everything about her life of vice, but he forgives her and asks Fanny to marry him, which she does.