Johnny Mnemonic was a data trafficker who has undergone cybernetic surgery to have a data storage system implanted in his head. The system allows him to store digital data too sensitive to risk transmission on computer networks. To keep the cargo secure, the data is locked by a password known only to the intended recipient. Johnny enters a trance-like state while the data is being transferred or the passwords are being exchanged, making him unaware of the contents and unable to retrieve it. He makes a modest living in the Sprawl by physically transporting sensitive information for corporations, underworld crime rings or wealthy individuals.

Johnny has arranged to meet with his most recent customer, Ralfi Face, at the Drome bar. Ralfi has stashed hundreds of megabytes of data in Johnny, and is overdue paying for the storage. To add to his troubles, Johnny has learned that Ralfi has placed a contract on him, although the reasons are unclear. Johnny finds Ralfi at his usual table, accompanied by a muscle man. Johnny threatens them with a sawed-off shotgun in his bag, but is incapacitated by a neural disruption device hidden under the table. Ralfi reveals that the data was, unknown to him at the time, stolen from the Yakuza, who are very interested in ensuring it is not revealed.

Johnny is rescued by Molly Millions, a "Razorgirl". She joins the action at the table, looking for a job. When attacked by the muscle man she cuts his wrist tendons and takes the incapacitating device control from him. Ralfi offers to pay her off, but she turns off the device anyway and frees Johnny. Johnny immediately offers a higher bid to hire her as a bodyguard. Johnny and Molly take Ralfi as they exit the bar, but then Ralfi is killed by a Yakuza contract killer, who dismembers Ralfi with a monomolecular wire sharper than any knife. Johnny fires the shotgun ineffectually, while Molly is delighted to be up against a pro.

Johnny decides that the only way to save himself from the same fate is to get the data out of his head with a SQUID. She leads him to an amusement park to visit Jones, a retired "navy dolphin" who was to locate and then hack enemy mines using sensors implanted in his skull, including a SQUID. To keep them loyal, the Navy addicted all of their "war whales" to heroin, so Molly trades Jones some heroin in exchange for retrieving the password. Armed with the password, Johnny has Molly read it to him in order to enter the retrieval trance, recording everything that is returned. After downloading the data, Johnny uploads a snippet to a Yakuza communications satellite, with the implication that the rest will be released if he is not left alone.

This leaves the more immediate threat of the Yakuza killer, who is unaware of the threat to release the data. Molly takes Johnny to the Lo Teks, anti-technology misfits who live in a suspended hideout high in the geodesic domes covering the Sprawl. Communicating via taut wires strung between the platforms, the Lo Teks are instructed to allow the killer to ascend the hideout to meet Molly on "The Killing Floor". Here, on a sprung floor that is wired to synthesizers and amplifiers, she dances around the killer while discordant noise blares from the soundsystem. Put off-guard by the strange environment, the killer eventually severs his own wrist, and then falls from the platform, happy to be free of the noise.

Johnny and Molly intend to make a living for themselves by using Jones to retrieve all the faint traces of all the previously stored data in Johnny, and blackmail his former customers with it, while living with the Lo Teks. However, sometime later, Johnny was assaulted in their appartment by the Yakuza and executed while Molly was out. When she returned she found him dead on the chair.