The novel begins as journalist Mikael Blomkvist attempts to exit through a crowd of eager reporters after his conviction for the libel and defamation of financier Hans-Erik Wennerström. Devastated by the verdict, Blomkvist retreats to a café and ponders his conviction. He anticipates three months in prison, but he worries more about the fate of his political magazine, Millennium. After thinking the matter over, he meets with Erika Berger, Millennium’s editor-in-chief and Blomkvist’s lover, and announces his intention to leave the magazine. In the meantime, Lisbeth Salander, an unorthodox young woman with piercings and tattoos who works for Milton Security’s private investigation division, attends a meeting with her boss, Dragan Armansky, and the lawyer Dirch Frode. Frode wishes to hire Blomkvist on behalf of Henrik Vanger, a wealthy industrialist and head of Vanger companies. Salander has compiled a report on Blomkvist and Frode wants to know the findings. Satisfied, he encourages Salander to continue her search into the Wennerström affair and calls Blomkvist to offer him the job.

Salander continues her research as requested and purchases an electronic cuff that will allow her to monitor Wennerström’s computer while Blomkvist considers the job offer. Burdened by concern for Millennium and his own career, Blomkvist agrees to meet Henrik on December 26th to hear the details. Henrik explains his family history and then, at length, presents the job offer: He wants Blomkvist to write a history of the Vanger family as pretext for solving the murder of Henrik’s great-niece, Harriet, who disappeared in 1966. Despite his interest in the mystery, Blomkvist feels reluctant to take the job since he has more important things to worry about. Henrik sweetens the pot, however, promising to give Blomkvist devastating information about Wennerström upon Blomkvist’s completing the job. As Millennium continues to lose advertising revenue, Blomkvist finally decides to take the offer as a way to repair the damage to his career.

Blomkvist makes the best of his situation in Hedeby, the small island where the Vanger family resides, and attempts to decipher five mysterious names and numbers in Harriet’s date book. Henrik also introduces him to the other members of the Vanger family. Meanwhile, Salander encounters a problem when her guardian, Holger Palmgren, becomes critically ill. The new guardian appointed for Salander, Nils Bjurman, threatens to control her finances, treats her with contempt, and forces her to perform oral sex on him. Furious, Salander decides to blackmail him and records their next encounter. The encounter doesn’t go as planned and Bjurman brutally rapes Salander. A week after the rape she returns to his home, handcuffs him to the bed, and tortures him while she threatens to publicize the recording of her rape. Ultimately she extracts Bjurman’s promise that he will permit her access to her finances and work to have her declared legally competent. Satisfied, she tattoos a reminder of his perversion on his abdomen and then leaves. She is surprised when she gets news that she is no longer needed to do research on the Wennerström affair.

Thanks to a helpful hint from his daughter, Pernilla, Blomkvist learns that the names and numbers in Harriet’s date book refer to Bible verses, not phone numbers. Desperate to solve the mystery, he asks Frode for another researcher, and Frode recommends Salander. After Blomkvist reads Salander’s report on him and discovers that she hacked into his computer, he visits her at home and begs for her help on the case. A wary, startled Salander complies and eventually the two discover that the names and numbers in Harriet’s date book reference a series of gruesome serial killings. As they research and grow intimate, an unidentified assailant fires shots at Blomkvist and leaves a dismembered stray cat on the porch. Convinced that the assaults confirm they’re close to a solution, Blomkvist tries to track down photographs of the Children’s Day parade from the day of Harriet’s disappearance. In the photos, Harriet is clearly dismayed, and Blomkvist hopes to discover who is causing her such distress. Salander departs for the Vanger family archives to make sense of small discrepancies in the serial killings, and Blomkvist finally finds his smoking gun: a photograph of Martin Vanger, Harriet’s brother, from the Children’s Day parade in 1966.

At the climax of the novel, Blomkvist goes to Martin’s cabin to confront him. Martin, prepared for his arrival, escorts him at gunpoint to a makeshift dungeon in the basement. Martin beats Blomkvist and then admits that both he and his father share responsibility for the killings and that they tried to induct Harriet into the murderous tradition as well. To Blomkvist’s surprise, however, Martin disavows any knowledge of what happened to Harriet and attempts to suffocate Blomkvist. Salander bursts in just in time and beats Martin severely with a golf club. He escapes as she frees Blomkvist from his bindings. Hurriedly Salander gives chase, but a desperate Martin drives his vehicle into the oncoming lane and dies in a fiery car accident. The next day, Salander, Blomkvist, and Frode agree that they will not notify the police about the murders. Putting together all the pieces, Blomkvist realizes that Harriet is not actually dead. He contacts her, and she shares her part of the story and reunites with Henrik. Later, when Frode informs Blomkvist that Henrik no longer wants to write the book and cannot offer any useful information on Wennerström—Blomkvist’s whole reason for undertaking the project—Blomkvist falls into despair. At that point, Salander offers up the information she’s collected about Wennerström’s corrupt financial dealings.

As the novel ends, Blomkvist writes an expose about the Wennerström affair that upends the financial world, restores his credibility, and reestablishes Millennium’s security. Salander assumes a fake identity and drains several of Wennerström’s accounts in order to secure financial independence in the future. Later, thanks to a tip from Salander, Wennerström resurfaces dead in a hotel room in Spain. Though Salander finally acknowledges her feelings for Blomkvist and prepares to confess them on Christmas, she finds him out with Millennium’s editor-in-chief, Erika Berger. Her decision to walk away from the situation indicates a lack of closure between the two of them despite their successful solving of the case.