In 2071, roughly fifty years after an accident with a hyperspace gateway made the Earth almost uninhabitable, humanity has colonized most of the rocky planets and moons of the Solar System. Amid a rising crime rate, the Inter Solar System Police (ISSP) set up a legalized contract system, in which registered bounty hunters, also referred to as "Cowboys", chase criminals and bring them in alive in return for a reward.

In the new Tokyo, where every fetish has a face, burned-out war photographer Tatsumi Saiga is slumming in the tabloid wasteland. Sent to dig up dirt on the underground elite, he stumbles upon a depraved ritual below the city—and before the night ends, a single kiss from a young beauty named Kagura Tennouzu ignites a chain of events that could force the entire ruling class to their knees.

Denizens of Lux have come to call it "The City" and treat it as a sentient force. Three factions vie for control of the city: the Organo, a strictly professional conglomerate with ties to the criminal underworld in the prosthetics business; the Union, a fanatical populist group interfering with Organo's affairs; and Racan, a marauding group of Texhnolyzed youths.

Japan has been invaded and conquered by the Britannian Empire. Japan is now known as Area 11 and its citizens known as Elevens. The Britannian Empire takes away Japan's autonomous power and imposes its rule through the use of Knightmares. The Empire's rule has never faltered, but cracks have begun to show...

Shinichiro is a student living in what would be a dream come true for most high school boys, but for him is mostly a frustration. A well liked girl in school named Hiromi has lived in his house for a year along with his family. Her father was a close friend of the family, and when he died they immediately took her in. She is popular and well liked, always smiles, is talented in sports- but Shinichiro knows there must be tears inside her. Having an artistic tendency, he makes watercolours of her and thinks about wishing to ease her tears. Yet he cannot bring up the nerve to talk to her even in his own home. She, too, is quiet and withdrawn in their house, quite unlike at school. Shinichiro is also distracted by teasing from his friend Nobuse for watching Hiromi from afar, a curse of bad luck from a strange girl named Noe, and being forced to perform Muhiga dancing. By helping Noe he hopes to ease his own problems, yet he seems to have difficulty helping himself.

In the future when technological enhancements and robotics are a way of life, Major Motoko Kusanagi and Section 9 take care of the jobs that are too difficult for the police. Section 9 employs hackers, sharpshooters, detectives and cyborgs all in an effort to thwart cyber criminals and their plans to attack the innocent.