Mysterio's history is presumably similar to his Earth-616 counterpart's up to the point where Spider-Man first bonded to the Venom symbiote. When Spider-Man began killing criminals, Mysterio and Spider-Man's other enemies reassembled the Sinister Six to stop him. They all agreed not to make a move until Kraven the Hunter made a battle plan.
Mysterio lured Spider-Man out to a remote location by sending out Beetle to feed Spider-Man info about the Sinister Six's location. When Spider-Man arrived, Mysterio used Image Inducers to produce illusions to terrorize Spider-Man while he and the Sinister Six wore glasses that filtered out the illusions. However, Spider-Man hid underground and launched a sneak attack. He shattered Mysterio's fishbowl helmet and killed him with biomass tentacles.