Ripper is set in New York City in 2040. The game opens with the investigation of the third murder attributed to a killer known as The Ripper — a name chosen for the methodological similarity to Jack the Ripper. Jake Quinlan, a reporter for the Virtual Herald, receives messages from The Ripper directly detailing each killing, and works alongside Detective Vincent Magnotta's police investigation to identify the perpetrator.
After examining Renee Stein's murder, Quinlan receives a warning from The Ripper: his girlfriend, Catherine Powell, will be the next victim because she has gotten too close to discovering the killer's identity. Quinlan finds Powell alive but in a coma no conventional medicine can penetrate. Cybersurgeon Claire Burton at the Meta-Cognition Center retrieves a distorted image of Powell's attacker from her memory, and Quinlan must gather enough information to clarify it.
The investigation leads to the discovery that everyone connected to the Ripper murders — victims and investigators alike, except Quinlan — shared a history with a gaming group called the Web Runners, who once played a game based on the Jack the Ripper mystery. The final session of that game caused one player to die in reality. That player was Catherine Powell's mother.
A pathologist named Vic Farley reveals the murder method: a code injected into a victim's brain through cyberspace that causes fatal internal pressure buildup. Quinlan locates a cyberspace weapon designed specifically to kill The Ripper inside a virtual reconstruction of Whitechapel, and uses it to end the case. The game's killer is drawn from four possible suspects — Joey Falconetti, Claire Burton, Vincent Magnotta, or Catherine Powell — with clues pointing toward each regardless of who is ultimately guilty.