Doctor Otto Gunther Octavius was introduced to Peter Parker when Harry Osborn invited Peter to meet Octavius, due to Parker needing to complete a project. A few days later Doctor Octavius had a presentation, introducing his plan to harness the element tritium to create clean fusion power. For the demonstration, Octavius built mechanical radiation proof arms, attached to his torso. When the fusion power machine malfunctioned, the inhibitor chip that prevented the AI in his mechanical arms from controlling him was destroyed.
Without the inhibitor chip, Doctor Octavius was being controlled by his arms. The arms got Octavius to think that doing the fusion experiment again was a good idea. After a bank robbery to get enough money to try the experiment again, Doctor Octopus realized that he would need more Tritium as well. He then went to the Osborn's residence, To take the Tritium from Harry Osborn, but Harry would only give it to Ock if he brought him Spider-Man alive. Ock finds Peter Parker and tells him to find Spider-Man or else he would kill Mary Jane Watson. Peter turns into Spider-Man and fights Doc Ock. They fall onto a moving train, which Ock sends toward unfinished track. Spider-Man stops the train, but Doctor Octopus knocks Spider-Man unconscious, then delivers him to Harry, who then gives Doc Ock the tritium. After turnng on the fusion power machine, Spider-Man arrives and fights with Doc Ock. Then Peter helps Octavius realize that his machine would destroy New York unless it was stopped. He then wills the mechanical arms to obey him, and sacrifices his life to drown the machine in the river.
Spider-Man: No Way Home
Otto was brought back to life and pulled into an alternate universe by Doctor Strange, who was casting a spell designed to erase everyone's knowledge that Spider-Man was Peter Parker, but due to that universe's Peter Parker's interference pulled in people from other universes who knew that Spider-Man was Peter Parker. The arms' AI took over once again and the Doctor Octopus persona re-asserted itself as he tries to find the fusion reactor. He encountered that universe's Peter Parker, but not knowing what happened demanded to know what happened to the reactor as he attacked him. The fight ended in Peter gaining control of the mechanical arms when the nano-technology in his suit integrated with them. As a restrained Doctor Octopus tried to make sense of what had happened, they were interrupted by the arrival of Norman Osborn/Green Goblin, whom Otto recognized, before they were transported into the Sanctum Sanctorum by Doctor Strange, who placed Doctor Octopus in captivity.
While imprisoned, Otto was introduces to that universe's Peter Parker friends, Ned and MJ. Although annoyed and confused about his predicament, Otto gives information about Norman Osborn to that universe Spider-Man and his friends, and that he died a long time ago. After Spider-Man found Electro and Sandman, Otto was surpised that the Lizard, who was captured around the same time he was, was a man from another universe. When Spider-Man brought Norman Osborn, Otto was shocked to see his friend alive as he asked him as to what happen to him, after seeing his tentacles. Otto tells Norman that he's the walking corpse as he becomes confused and dosen't believe his story until Sandman told him the truth, and that Doctor Octopus also died a couple of years after Norman did. After the current universe Peter Parker stopped Doctor Strange from sending everyone home to meet thier fates, Doctor Octopus was suprised that he didn't let him and the rest of the villians to die or be defeated by their Spider-Men as he questioned him as to why with MJ telling him that its not who he is.
After Parker freed them of their imprisonment, Doctor Octopus was forced to join the other villains as he was brought to a friend of the current universe Spider-Man's place.
Upon arriving, Doctor Octopus was informed that he'll be the first to be worked on as he protested that he doesn't need fixing. Doctor Octopus had to suffer from being bided by his own tentacles as he waits for the current universe Peter Parker and Norman. After the current universe Peter Parker and Norman finished making a new inhibitor chip for him by using Stark Industries technology, Doctor Octopus was struggling when Spider-Man put the new chip on the back of his neck but was able to successful. Through the new inhibitor chip, Otto was finally free from his tentacles control and showed his gratitude to the current universe Peter Parker for giving him his mind back. Otto offers his help to the current universe Peter Parker and Norman in curing the rest of the villians, even his old friend.
However, when the Green Goblin persona took over Norman, Otto attempted to help but was incapacitated by Max Dillon/Electro. Otto fell out of the building, but his tentacles broke his fall but had no choice to retreat for the time being. Later, Otto intervened in the final battle at the Statue of Liberty by tricking Electro and the other Peter Parkers into thinking he was once again Doctor Octopus, only to use his arms to attach Dillon's cure to him and remove the arc reactor. Otto stared at it in wonder, amazed that someone in this universe had achieved what he hadn't: "the power of the sun in the palm of [his] hand." Hearing a familiar voice, Otto realized that his Peter Parker was also brought to the new universe as he has an emotional reunion with him and was amazed to see how grown up he is in the time since they had last met. When the Green Goblin reappeared, Otto tried to stop him from destroying the box that can send everyone back to their universes but he ended up using one of his pumpkin bombs. Seeing that the explosion caused the reconstruction of the statue of liberty to collapse, Otto brings the now cured Max Dillion to safety. When Doctor Strange cast a new spell that will erased everyone in that universe knowledge of Spider-Man's identity, Otto, Norman, Flint Marko and their Peter were sent back to their universe just before the spell was completed, with his fate completely changed.