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The first encounter of Mayhem was by Fernando the janitor was attacked by Mayhem when he came out of a vent and started tossing him around the room the only reason Fernando survived the encounter was by Jonathan the theatre man whose screams scared Mayhem away. The Ghostbusters then came and investigated the scene. Abby then found a Hyper-Ionization Device, which mostly likely caused caused Mayhem to appear. Patty then had an experience with a mannequin that was possessed by Mayhem. Patty Tolan then came running through the door to the room where Abby found the Hyper-Ionization device where she met up with the other Ghostbusters. Suddenly the mannequin (still possessed by Mayhem) breaks the door causing the Ghostbusters to fire their proton beams at him after a few seconds the mannequin breaks revealing his true form he then flies down the hall he then went up through a vent.
Mayhem then appeared on the stage of the concert with the band "Beasts of Mayhem" who had thought he was a special effect. A few seconds Mayhem threw the lead singer into a stack of speakers. Moments later the Ghostbusters come onto the stage via backstage and start firing at Mayhem. They start firing away hitting some decor. Then two of the Ghostbusters Abby Yates and Patty Tolan leave the stage to hunt Mayhem. Patty while getting off the stage falls and finds Mayhem on her shoulders. Patty tried to get him off but Abby decides to fire at him so the other two Ghostbusters joined in he eventually got off and Patty started firing at him then Jillian laid down the Ghost Trap everyone steered him towards the trap and he was successfully trapped.
When Dr. Martin Heiss goes to the Ghostbusters H.Q. he questioned the Ghostbusters on why they were making these "fake" ghosts. Erin then releases Mayhem causing him to grab Dr. Heiss and throw him out the window making Mayhem free again.
During the Battle for Times Square Mayhem attacks Abby dragging her away until Erin shoots him with a proton stream he then later attacks Jillian but Patty is prepared with her Ghost Chipper killing Mayhem.
- His skin colour was first seen as blue but then in-game, his skin colour changes to green, which is the same as in the movie.