Case is a matrix (cyberspace) cowboy (paid hacker/data thief). Several years ago he was caught stealing and the punishment was to have a chemical burn to his brain that resulted in him no longer being able to jack into the matrix. Now he spends his time in Chibi, Japan running drugs and other illegal items. His also a drug addict. His girlfriend tells him that there is a hit out on his head, but when he confronts the supposed person, he discovers this is a lie. His girlfriend, meanwhile, stole some RAM to sell on the black market.

When Case returns to his sleeping cube, he finds a woman there (Molly) who has permanent mirrored eyes and blades in her fingernails. She brings him to Armitage (former military) who offers to cure the brain damage if Case will do a run for him. Case agrees, has the surgery to fix his brain, and joins the group. While waiting to recover, he goes to a gladiator event with Molly where his former girlfriend is murdered. Case also discovers he can no longer take drugs. His first job is to steal the ROM (or saved consciousness) of a former hacker named the Dixie Flatline (also called the Construct).

Working behind Armitage's back, Molly, Case and Dixie discover that Armitage was the only survivor of a military hack against Russia and is now being controlled by an AI named Wintermute. Wintermute soon contacts Case through the guise of other people Case knows. Next, the group gets the help of a man named Peter Riviera, a drug addict who can project detailed holographic images to everyone around him.

The group's ultimate mission is to enter the Tessier-Ashpool facility to combine Wintermute with another AI named Neuromancer. Wintermute wants this done because the Turing Laws prevent it from acting with completely free will. Riviera worms his way into the TA facility and lets Molly in who must sneak and fight her way to a central chamber where she will manually give a command to a terminal while Case hacks in through the Matrix.

The complicated plan succeeds, but only through Case physically bringing his deck to into the facility and jacking in from there. Wintermute and Neuromancer merge, but as far as Case can tell nothing changes. He and Molly part ways. The novel ends with Wintermute/Neuromance contacting Case and mentioning that he is searching for other AIs (one he already found from a transmission from Alpha Centauri). There is an implication that Dixie was not erased as he wished but is still "alive" in the Matrix.