The story takes place in the year 2034, two years after the events in Ghost in the Shell: S.A.C. 2nd GIG. Female cyborg Major Motoko Kusanagi has left Public Security Section 9, an elite counter-terrorist and anti-crime unit specializing in cyber-warfare, which has expanded to a team of 20 field operatives with Togusa acting as the field lead.

Cyborg detective Batou is assigned to investigate a series of murders committed by gynoids—doll-like cyborgs, which all malfunctioned, killed, then self-destructed afterwards. The brains of the gynoids initialize in order to protect their manufacturer's software, but in one gynoid, which Batou himself neutralized, one file remains: a voice speaking the phrase "Help me."

In the year 2029, the barriers of our world have been broken down by the net and by cybernetics, but this brings new vulnerability to humans in the form of brain-hacking. When a highly-wanted hacker known as 'The Puppetmaster' begins involving them in politics, Section 9, a group of cybernetically enhanced cops, are called in to investigate and stop the Puppetmaster.