Part One

The story starts with a fictional foreword by one John Ray Jr., PhD, an editor of psychology books. In it, Ray writes that he's presenting the details of a memoir entitled The Confession of a White Widowed Male written by a literary scholar of mixed European ethnicity who died recently in an American jail of heart failure while awaiting his murder trial. The memoir's author uses the pseudonym Humbert Humbert to refer to himself in the manuscript. Humbert begins the memoir with his Parisian childhood and ends it with his incarceration. The story is told entirely from Humbert's perspective. Ray says he received the memoir from Humbert's lawyer, C.C. Clark, and adds that he (Ray) has changed the names of the people mentioned in it to protect their identities except for one: "Lolita"; the nickname Humbert used to refer to the young girl with whom he was sexually obsessed. Ray notes that Lolita died in 1952 while giving birth to a stillborn girl on Christmas Day while married to Richard Schiller, presumably the father of her child.

After losing his mother at a young age, Humbert has a rich childhood living in his wealthy father's hotel. At the age of 13 Humbert has a precocious relationship with a girl his age, Annabel Leigh, but her family moves away before they get the chance to have full sex. Annabel dies shortly thereafter of typhus. Following this, Humbert finds he has a hebephilic fixation with certain girls ages 9 to 14 which he identifies as nymphets. He claims the cause of his fixation is an unconsumated sexual encounter with someone of the same age when he was a child.

Humbert visits many prostitutes as a young adult but is unsatisfied unless they resemble a nymphet. He eventually marries a Polish woman named Valeria to allay suspicion of his hebephilia. Humbert plans on migrating to America and leaving her after several years of marriage, only for the marriage to dissolve anyway after she admits to having an affair. Later, Humbert suffers a mental breakdown and recovers in a psychiatric hospital. Upon his release, he moves to the United States to write, living off an allowance left by a wealthy uncle in return for writing perfume adverts. After a year attached to an arctic expedition, the only time in his life he claims to have been free of his tortured yearning, Humbert suffers another mental breakdown, and learns to manipulate psychiatrists while he recovers.

Relieved of his perfume duties while still entitled to the allowance, Humbert plans to move to South America to take advantage of looser laws concerning the age of consent. However he's offered to board and lodge with the McCoo family, living in the fictional New England town of Ramsdale, and he accepts purely because they have a 12 year-old daughter whom he plans to spy on. Upon his arrival he discovers that their house has burned down; Charlotte Haze, a wealthy Ramsdale widow, offers to accommodate him instead and Humbert visits her residence out of politeness. He initially plans to decline Charlotte's offer but agrees to rent when he sees her 12-year-old daughter, Dolores, whom Charlotte calls Lo. Humbert is instantly smitten, and fantasizes constantly about Lo. Charlotte and Dolores have a poisonous relationship and frequently argue, while Humbert finds himself growing infatuated with Dolores and privately nicknames her Lolita. Over the course of a single month Humbert's entire life comes to revolve around masturbating to Lolita. He starts a diary in which he records his obsessive fantasies about Dolores, while also expressing his loathing for Charlotte whom he sees as an obstacle to his passion. One Sunday morning, while Charlotte is out of the house, Dolores and Humbert engage in a somewhat flirtatious interaction, ending with Lolita sitting on Humbert's knee. Humbert uses the interaction to bring himself to ejaculate, which Dolores does not apparently notice.

Charlotte decides to send Dolores to summer camp, where she will stay for three weeks. On the day of leaving, Lolita runs back upstairs and kisses Humbert on the lips, before returning to the car. The housemaid gives Humbert a letter from Charlotte shortly thereafter, in which she confesses that she has fallen in love with him. She adds that if he doesn't love her back he must move out immediately. Humbert's solution to this dilemma is to marry Charlotte, for purely instrumental reasons – it will let him stay close to Dolores and even let him innocently fondle her out of feigned paternalism. Later, Charlotte voices her plan to send Dolores to a boarding school when she returns from camp. Humbert contemplates murdering Charlotte to remain close to Dolores, and even comes close to drowning her in the town lake, but stops before carrying it out. Humbert instead acquires strong sedatives from the town doctor, planning to put both Hazes to sleep so that he can molest Dolores in the night. A few days later however, Charlotte finds Humbert's diary and furiously confronts him, telling him he will never see Dolores again. While Humbert prepares a drink for her, Charlotte runs out of the house to mail letters she's written to friends about Humbert's lust for Dolores, but is killed by a swerving car. Humbert recovers the letters from the accident scene and destroys them. Later, he convinces Charlotte's friends and neighbors that he should look after Dolores as he is now her stepfather.

Humbert retrieves Dolores from camp and lies to her, telling her that Charlotte is ill and has been hospitalized. He then takes her to a high-end hotel that Charlotte had earlier recommended. Humbert feels guilty about consciously raping her, and so tricks her into taking the sedatives in her ice cream. As he waits for the pill to take effect he wanders through the hotel and meets an anonymous man who, he does not know, is in fact famous playwright Clare Quilty, a friend of the now-deceased Charlotte. Quilty recognises Dolores, and without revealing anything talks ambiguously to Humbert about his "daughter". Humbert excuses himself from the conversation and returns to the hotel room. There, he discovers that the doctor fobbed him with a milder drug, as Dolores is merely drowsy and wakes up frequently, drifting in and out of sleep. He dares not touch her that night. In the morning, Lo reveals to Humbert that she actually has already lost her virginity, having engaged in sexual activity with an older boy at a different camp a year ago at age 11. Humbert tricks her into believing that he has no knowledge of sex play and it is not something that adults do. She wants to show him, and so the two have sex. While driving the next day, Dolores is ambiguously uncomfortable and insists on calling her mother from a pay phone; it is only then that Humbert finally reveals to Dolores that her mother is dead.

Part Two

Humbert and Dolores begin traveling across the country, driving all day and staying in motels. To keep Dolores from going to the police or running away, Humbert points out she would likely wind up in a state-run orphanage if she leaves him, a prospect which terrifies her. He manipulates her with gifts of money and clothing in return for sexual favors. Completely paranoid about the situation and increasingly jealous of her flirtations with others, Humbert controls Dolores's movements carefully and forbids her from associating with other teenagers. After a year of touring the United States, Dolores pressures Humbert to settle, and so he takes her to the (fictional) New England town of Beardsley, where he enrolls her in the local girls' school. Humbert reluctantly grants Dolores permission to join the school play which, unbeknownst to Humbert, was written by Quilty. The living situation between the two grows increasingly tense, erupting into a row before the play's opening night. Humbert grabs Dolores by the wrist and injures her during the quarrel, and while he's distracted by a neighbour she flees the apartment. Humbert chases after her and finds her using a pay phone in a drug store. While talking to her, Humbert finds that Dolores has had a complete change of heart. She decides not to participate in the school play and asks Humbert to take her on another cross-country trip. Humbert eagerly agrees. Back at the apartment, Lo is unusually flirtatious and the two have sex once more.

While on their second road trip, Humbert becomes suspicious that a driver is following them. He swears he sees Dolores talking to a man he barely recognises driving a conspicuous red car, and on another occasion Dolores seems to sabotage his effort to confront the man. Later, Humbert leaves Dolores in a Texas hotel to run errands, returning to discover Dolores's hair disheveled and her make up smudged. He strongly suspects she has had sex with another man while he was out but he has no way to prove it. In the Colorado mountains, Dolores falls ill and Humbert checks her into a hospital while he stays in a nearby motel. After several days, he contacts a nurse at the hospital to inquire about Dolores's condition; he is surprised when the nurse tells him that she has already checked out. An "uncle" has paid her bill and taken her to her "grandfather"'s home; Humbert knows Lolita has no living relatives and he immediately embarks on a frantic search to find Dolores and her abductor, but ultimately fails.

For the next two years, Humbert barely sustains himself in a moderately-functional relationship with a notorious Californian alcoholic named Rita. Deeply depressed, Humbert receives a letter from the residents of Ramsdale, who have learnt that Dolores has gone missing and are pressing for answers. Knowing that his situation is precarious and contemplating what to do, Humbert eventually receives another letter – it's from Dolores, now 17, telling him that she is married, pregnant, and in desperate need of money. Dolores tells him to deliver $400 cash to her residence in the town of Coalmont, where she lives with her husband, Richard Schiller. She did not provide Humbert with her street address. Humbert nevertheless immediately leaves New York for Coalmont; he believes Schiller is the abductor and plans to murder him as soon as possible. He tracks down Dolores and finds her living in a clapboard house with her husband, who is not the abductor. Humbert and Dolores awkwardly discuss her new married life, Dolores passing Humbert as her real father to her husband and cheerily pretending their past never happened. Humbert no longer feels any sexual attraction to the now-matured Dolores, but nevertheless realizes he's still in love with her. He gives her ten times as much money as she asked for, and then asks her to abandon this life and leave with him. She accepts the money but firmly declines the offer of a life together. As he is leaving, Dolores reveals to Humbert that it was Quilty who took her from the hospital, and that she willingly left because she was in love with him. After moving into his mansion in Ramsdale for a period, Quilty tried to make her star in one of his pornographic films. She refused, and so he expelled her from his home. Afterward, she supported herself by working as a waitress. Humbert leaves in tears, resolving to track down and kill Quilty.

Returning to Ramsdale, Humbert visits Quilty's uncle, who is a local dentist, and learns the location of Quilty's mansion. Humbert arrives at the mansion to find a hedonistic lair with the front door unlocked, and Quilty under the influence of drugs. Quilty at first thinks Humbert is an electricity man, then just another actor or socialite taking advantage of his generosity. Even after revealing himself and his purpose, Quilty still barely takes Humbert seriously and only after a few tussles does he attempt to talk down Humbert from killing him. Eventually Humbert shoots Quilty in a chase around the mansion; he leaves as a large number of Quilty's guests arrive, who also do not take the idea of Quilty's murder seriously. Later, Humbert allows himself to be captured by police while driving recklessly in a daze around Ramsdale.

In his closing thoughts, Humbert expresses his belief that he is guilty of statutory rape, but all other charges against himself should be dismissed. He reaffirms his love for Lolita, and asks for his Confession to be withheld from public release until after her death.

Lolita is frequently described as an "erotic novel", both by some critics but also in a standard reference work on literature Facts on File: Companion to the American Short Story. The Great Soviet Encyclopedia called Lolita "an experiment in combining an erotic novel with an instructive novel of manners". The same description of the novel is found in Desmond Morris's reference work The Book of Ages. A survey of books for Women's Studies courses describes it as a "tongue-in-cheek erotic novel". Books focused on the history of erotic literature such as Michael Perkins' The Secret Record: Modern Erotic Literature also so classify Lolita.

More cautious classifications have included a "novel with erotic motifs" or one of "a number of works of classical erotic literature and art, and to novels that contain elements of eroticism, like ... Ulysses and Lady Chatterley's Lover".

This classification has been disputed. Malcolm Bradbury writes "at first famous as an erotic novel, Lolita soon won its way as a literary one—a late modernist distillation of the whole crucial mythology." Samuel Schuman says that Nabokov "is a surrealist, linked to Gogol, Dostoyevsky, and Kafka. Lolita is characterized by irony and sarcasm; it is not an erotic novel."

Lance Olsen writes: "The first 13 chapters of the text, culminating with the oft-cited scene of Lo unwittingly stretching her legs across Humbert's excited lap ... are the only chapters suggestive of the erotic." Nabokov himself observes in the novel's afterword that a few readers were "misled.  ... into assuming this was going to be a lewd book ... the rising succession of erotic scenes; when these stopped, the readers stopped, too, and felt bored."

The novel is narrated by Humbert, who riddles the narrative with word play and his wry observ