The novel begins in Chiba. Case, a former console cowboy, now works as a middleman for smugglers and drug dealers. Case misses his old job, but was forced out after stealing from his bosses, who punished him by destroying his nervous system, preventing him from ever jacking into the matrix again. Case hoped to find a cure in Japan, but ran out of money, and now lives on the edge of society. Drug-addicted and indebted to his employers, Case is aware he does not have much time left before his lifestyle catches up with him. He runs into his ex, Linda Lee, who he introduced to drugs during their brief relationship. He still loves her, and gives her what little money he has, but when he returns to the coffin where he stores trafficked goods, he realizes she’s stolen some important data that he had been hoping to sell to pay his debts.
Case’s luck changes when Molly approaches him. Molly is a razorgirl who works for Armitage, a mysterious ex-military point man, whose secret and shady employer has tasked him with assembling a team to carry off a series of heists. Armitage promises to restore Case’s nervous system, allowing him to jack into the matrix once again, and Case immediately signs on.
The trio travels to the Sprawl, where they pull off their first mission—extracting the late Dixie Flatline’s construct from the libraries of the corporation Sense/Net. Case works behind the scenes, creating a virus that can break through Sense/Net’s digital defenses, while Molly acts as the muscle, physically breaking into the building and stealing the construct.
Next, the group travels to Istanbul, where they recruit/kidnap Peter Riviera, a psychopath who has implants that allow him to create life-like holographic hallucinations. Once he’s on board, the four of them—Armitage, Case, Molly, and Riviera—travel into space, first to Zion and then to Freeside, where their mission really begins.
Molly has been suspicious of Armitage and his secret employer from the beginning, and so, with Case’s help, begins to research her boss on the side. They discover his real name is Corto, and that Armitage is a completely fabricated persona. The real man, Corto, was brutally disfigured during a military operation, Screaming Fist, and was rebuilt first by the United States Government, and then by Wintermute, an AI who has been manipulating Armitage all along. Wintermute is one of two AIs belonging to the Tessier-Ashpool family (the other one, Neuromancer, gives the novel its name). Wintermute wants Armitage and his team to infiltrate the Tessier-Ashpool compound, the Villa Straylight, and cut certain restrictions placed on Wintermute, which will allow it to combine with its sibling, Neuromancer, into an even more powerful AI.
Although their mission is straightforward in theory, Case and Molly, with whom he has developed a sexual, if not romantic relationship, must avoid law enforcement and also battle Riviera (who turns against them), Armitage (who loses his mind), and manipulative AIs. Molly physically breaks into the Villa Straylight, only to be captured by Riviera, 3Jane, a member of the Tessier-Ashpool family, and her cloned bodyguard, Hideo. Case, with the help of Maelcum, a pilot and Zionite, rescues Molly and completes their mission but not before being trapped in cyberspace by Neuromancer, who desperately wants to remain separate from Wintermute. Neuromancer uses a digital replica of Linda Lee to entice Case, hoping to keep him in cyberspace voluntarily, but he escapes. Together Case, Molly, Maelcum, and Wintermute break through Wintermute’s chains, allowing the AI to escape and evolve, joining with Neuromancer and becoming as vast and powerful as the matrix itself.
