The novel's fictional "Foreword" states that Humbert Humbert dies of coronary thrombosis upon finishing his manuscript, the events of the novel. It also states that Mrs. Richard Schiller [Lolita] died giving birth to a stillborn girl on Christmas Day, 1952, at the age of 17.

Humbert Humbert, a literary scholar, has harboured a long-time obsession with young girls, or "nymphets". He suggests that this was caused by the premature death of a childhood sweetheart, Annabel Leigh. After an unsuccessful marriage and having recovered from a mental breakdown, Humbert moves to the small New England town of Ramsdale to write. He rents a room in the house of Charlotte Haze, a widow. Humbert also meets her 12-year-old daughter, Dolores (born 1935[1]), known as "Lo", "Lola", or "Dolly", with whom he immediately becomes infatuated, partly due to her uncanny resemblance to Annabel, and privately nicknames her "Lolita". Humbert stays at the house only to remain near her.

While Dolores is away at summer camp, Charlotte, who has fallen in love with Humbert, tells him that he must either marry her or move out. Humbert agrees to marry Charlotte in order to continue living near Lolita. Charlotte is oblivious to Humbert's distaste for her, as well as his lust for Lolita, until she reads his diary. Learning of Humbert's true feelings and intentions, Charlotte plans to flee and send Lolita to a reform school, threatening to expose Humbert as a "detestable, abominable, criminal fraud." However, fate intervenes on Humbert's behalf: as she runs across the street in a state of shock, Charlotte is struck and killed by a passing car.

Humbert picks Lolita up from camp, pretending that Charlotte has been hospitalised. Rather than return to Charlotte's home, Humbert takes Lolita to a hotel, where he gives her sleeping pills. As he waits for the pills to take effect, he wanders through the hotel and meets a man who seems to know who he is. Humbert excuses himself from the strange conversation and returns to the room. There, he tries molesting Lolita but finds that the sedative is too mild. Instead, she initiates sex the next morning, after explaining that she had slept with a boy at camp. Later, Humbert reveals to Lolita that Charlotte is dead, giving her no choice but to accept her stepfather into her life on his terms or face foster care.

Lolita and Humbert drive around the country, moving from state to state and motel to motel. In order to keep Lolita from going to the police, Humbert tells her if he is arrested, she will become a ward of the state and lose all her clothes and belongings. He also bribes her for sexual favours, though he knows that she does not reciprocate his love and shares none of his interests. After a year touring North America, the two settle down in another New England town, where Lolita is enrolled in a girls school. Humbert becomes very possessive and strict, forbidding Lolita to take part in after-school activities or to associate with boys. However, most of the townspeople see this as the action of a loving and concerned, though old-fashioned, parent.

Lolita begs to be allowed to take part in the school play, and Humbert reluctantly grants his permission in exchange for more sexual favours. The play is written by Clare Quilty. He is said to have attended a rehearsal and been impressed by Lolita's acting. Just before opening night, Lolita and Humbert have a ferocious argument, and Lolita runs away while Humbert assures the neighbours everything is fine. He searches frantically until he finds her exiting a phone booth. She is in a bright, pleasant mood, saying that she tried to reach him at home and that a "great decision has been made." They go to buy drinks and Lolita tells Humbert she doesn't care about the play and wants to resume their travels.

As Lolita and Humbert drive westward again, Humbert gets