Henry Dorsett Case, also known as "Case," is a former "console cowboy"—a hacker—living on the outskirts of Chiba City, Japan in a dystopian, gritty future. The world has transformed into a conglomeration of urban sprawls, many of which are overrun by crime; gangs, mafia, drug peddlers, cybercriminals, and black-market dealers dominate the cities. Case longs to return to hacking but is unable to because one of his bosses suspected him of theft and had his nervous system damaged by mycotoxins, thus stripping him of his ability to "jack" into the "matrix" (cyberspace). As Case roams the city, his ex-girlfriend, Linda Lee, is killed in front of him in an altercation that takes place within an arcade.
Case realizes he's being tailed; it's Molly Millions, a "razorgirl" with a series of body modifications known as cybernetic implants, and she tells him he's being recruited for a secret cyber-hacking mission. She takes him to meet her boss: Armitage, a mysterious US ex-military officer, who promises Case that he will give him back his ability to hack into the matrix if he agrees to take on the mission. Case agrees and Armitage restores Case's spinal nervous system. However, he reveals that he has placed toxic sacs into Case's spine; if Case does not fulfill the mission, the sacs will slowly dissolve and kill Case.
Armitage asks Case and Molly to steal a ROM containing the memory of Dixie Flatline, a cyber cowboy also known as McCoy Pauley who served as one of Case's former mentors. The ROM is located in Sense/Net, a network that belongs to the Tessier-Ashpool family—a vast family-controlled corporation also known as Tessier-Ashpool SA. Case and Molly succeed in stealing the ROM. Armitage reveals that he is assembling a "team" for a larger mission.
Behind Armitage's back, Case and Molly discover Armitage's secret identity as Colonel Willis Corto. Corto was part of a high-level military operation known as Operation Screaming Fist. During a mission trying to hack into Soviet computer networks, his aircraft was shot out of the air by Russian intercepting planes. All members of the operation other than Corto were killed. Corto survived by crawling across the Finnish border. Extremely traumatized by the accident, Corto began a life of crime, making his way through Europe and eventually landing in a Parisian psychiatric hospital. After some months, a government official came and took Corto back to the United States. The government agreed to restore Corto's sight and severed legs but only so that he could testify in a sham trial that is meant to cast the government in a positive light after the disaster.
Case, Molly, and Armitage travel to Istanbul in order to recruit a drug addict and known thief, Peter Riviera, for Armitage's team. Riviera is regarded as a "sociopath" and uses his cybernetic implants to cast holograms that often manipulate others and prey upon their insecurities. Case is contacted by the enigmatic AI Wintermute. In pursuit of Wintermute, Case and Molly go to Freeside, a space station created and run by Tessier-Ashpool SA. With the help of Dixie Flatline's ROM, Case continues to converse with Wintermute, which confesses that its only desire is to unite with another AI developed by Tessier-Ashpool in order to form a "superintelligence." Wintermute reveals that it exploited Corto and took him out of the psychiatric hospital in order to construct the Armitage persona over Corto's shattered psyche, thus turning him into a manipulatable pawn for its plan to find the other AI. Acting on Wintermute's orders, Armitage set out to construct the team that Molly and Case now find themselves a part of. Riviera has been instructed to retrieve the password that will unlock the second AI from Lady 3Jane Marie-France Tessier-Ashpool, the CEO of the Tessier-Ashpool family and the third clone iteration of the daughter of the original founder, John Ashpool.
Case, Molly, and Armitage travel to Zion, another city, in order to recruit a pilot, Maelcum, and a ship for their mission, Marcus Garvey. They return to Freeside and Molly ventures into Villa Straylight, the Tessier-Ashpool home and headquarters. Molly enters the villa and finds John Ashpool, the former patriarch of the Tessier-Ashpool family and corporation. She kills him, with Case accompanying her through a technology known as "simstim" (simulation stimulation) that allows him to experience her reality through cyberspace. Molly goes deeper into the Villa, searching for Lady Jane, while Case continues to jack into the matrix from Marcus Garvey in order to monitor her and converse with Wintermute. On Marcus Garvey, Armitage's personality begins to fracture to reveal Corto, who is so unstable that Wintermute ejects him from the ship to prevent him from putting the mission in jeopardy.
In Villa Straylight, Molly is injured but manages to find Lady 3Jane. Riviera has double-crossed the team and now protects Lady 3Jane, alongside 3Jane's ninja bodyguard, Hideo. Simultaneously, Case finds himself in a simulated reality created by the second AI, Neuromancer. Neuromancer attempts to lure Case into staying within the simulation by "resurrecting" Linda Lee, Case's ex-girlfriend who was previously assassinated. Case jacks between the simulation, Marcus Garvey, and Villa Straylight, where Riviera attempts to kill Molly but is thwarted by Lady 3Jane, who sympathizes with Case and Molly. 3Jane explains that her mother had constructed the two AIs in the hopes of fostering a symbiotic relationship between the Tessier-Ashpools and the family. The collaboration could have ensured that the Tessier-Ashpools would grow infinitely powerful and immortal.
3Jane, Molly, and Case find the center of the AI computer and 3Jane gives up the password, setting Wintermute free to unite with Neuromancer. Case refuses to stay within Neuromancer's simulation because he realizes he cannot let go of the haunting doubt he has over whether Linda Lee is real or not. Molly and Case return to the Sprawl, and Case eventually goes back to Chiba City. Wintermute-Neuromancer, now a single superintelligence, contacts him to tell him that it has received messages from other AIs, who are located as far as the Alpha Centauri star system.
The novel concludes on a scene set within cyberspace. Case sees a boy—the form that Neuromancer adopted in the simulated reality—alongside Linda Lee. Case hears laughter, which potentially implies that Dixie Flatline/McCoy Pauley still exists in the matrix, although this remains a mystery. The ending itself ambiguously suggests that Case himself is a copy of the original, stored in a ROM like Dixie Flatline was.
