The Living Brain, soon after its creation, was brought to Midtown High School by its creator, Dr. Petty, as a part of a demonstration of its ability to solve any problem. After the Living Brain's demonstration, two workmen hired to transport it overheard the Living Brain's ability to answer anything, and decided to steal it, in order to use its abilities for gambling purposes.
Caught in the middle of stealing the Living Brain by Dr. Petty, the two workmen got into a scuffle with him, which ended with one of them being knocked into the control panel on the Living Brain's chest, which caused the Living Brain to malfunction. Going on a rampage through Midtown High, the Living Brain was eventually shut down by Spider-Man, who destroyed its control panel, in a brief fight.
The Living Brain reappeared several years later, discredited and broken-down. Dr. Petty planned to donate it to Midtown High School's science lab. The Living Brain ended up being stolen by Dr. Petty's son, Steve Petty, who modified the robot, giving it a gold and red color scheme, clawed hands and the ability to fly. Remotely controlling the Living Brain to attack a bully who had been tormenting him, Steve was eventually defeated by Spider-Man (who had been on a visit to Midtown High as Peter Parker) and the Living Brain was shut down once more.
Living Brain later preps Otto's lab for a "Parker-Ectomy."
When Spider-Island II is attacked by the Goblin Underground, the Superior Spider-Man gets Living Brain out and rides it away from Spider-Island II while evading the pursuers from the Goblin Underground. The Superior Spider-Man later uses Living Brain to help fight Monster (the Goblin form of Carlie Cooper).