Dr. Otto Octavius was a lab assistant to Norman Osborn and secretly a spy for Osborn's business rival, Justin Hammer. He was caught in a lab accident (the same one that turns Norman into the Green Goblin), grafting his traditional metal arms onto his body. After this incident, he was able to communicate with these mechanical arms via telepathy. He modified his arms to have the power to morph into different shapes, and then sought revenge against Justin Hammer, but Spider-Man intervened. Although Octavius was defeated by Spider-Man, Justin Hammer perished due to a heart attack caused by Doctor Octopus' attack.
Afterwards, Octavius was brought into S.H.I.E.L.D. custody where he, along with Norman Osborn, formed the Ultimate Six, comprised of Osborn, Electro, Kraven, Sandman, and later an unwilling Spider-Man himself. After breaking out of custody, they attack S.H.I.E.L.D. and capture Spider-Man. They take him to their hideout, tie him to a chair, and force him to join them. They then attack the white house. In a battle between the Six and the Ultimates on the White House lawn, Octopus was taken down by the Wasp. Octavius was separated from his tentacles and held in a different prison far away from them.
Octavius, in jail, later found out that his ex-wife was giving the rights to use his likeness in the Spider-Man film. Outraged, he summoned his tentacles from the S.H.I.E.L.D. facility and went on a rampage, murdering many people, until he was faced by Spider-Man. He defeated Spider-Man, hijacked a plane to Brazil, tied Spider-Man to one of the seats, unmasks him, and tortures him, until he escaped and defeats him. Back in S.H.I.E.L.D. custody, Nick Fury melted Doctor Octopus' mechanical arms in front of him and instructed the guards to watch the melting mechanism for at least an hour afterward to make sure the arms would not try to escape. However, a spare set of arms existed within a bunker belonging to Norman Osborn. Plans for these remain to be seen.
Otto Octavius was responsible for all the Spider-Man clones, including an older clone of Peter believing itself to be Richard Parker, Peter's father. His experimentation and research was done for the FBI in order to find a way to create super soldiers so the U.S. Government wouldn't have to be reliant on Nick Fury's monopoly on the Ultimates; he appeared alongside Fury, S.H.I.E.L.D. and the Fantastic Four in the storming of an Osborn Industries plant, and was outside Fury's jurisdiction.
Octavius was later working for the Roxxon Corporation and was the leader of the company's Brain Trust. He was working in response to the attacks on the company that were similarly committed on different locations such as the Baxter Building. After Spider-Woman was captured by Roxxon's Brain Trust, Otto reveals himself and informs them that he was there at Jessica's birth. He explain to his Brain Trust that Spider-Woman's involvement in the matter is unrelated to their investigation and clearly wanted for vengeance.
At this point, Spider-Man burst in, subduing Octavius and his Brain Trust, and freeing Spider-Woman. Thereafter Octavius was furiously beaten by Spider-Woman before being stopped by Spider-Man and together left Roxxon. Afterward, the same entity that attacked Roxxon had returned and crushed the building along with Octavius. Octavius was weighted down by the biomass while struggling to keep himself from being crush to death.
Fortunately, Spider-Man and along with a very reluctant Jessica Drew pulled him out before the biomass completely collapsed on the building, in which Octavius gratefully thanked for saving him. Thereafter, Johnny Storm and Rick Jones appeared before them and informed them the attack on Roxxon and the other invaluable locations were being committed by a mad Reed Richards. Upon hearing this, Octavius decided to come with them in stopping Richards as he reasoned that he knows well about him and claimed that he is the cause for ruining his (Octavius's) and Jessica Drew's lives, and as well for possibly killing his Brain Trust. Much to Spider-Man and Jessica Drew's chagrin, Octavius was immediately brought along and transported to Project Pegasus.
When Norman Osborn, the Green Goblin, escaped Triskelion, he took with him other five super villains, one of them being Octavius. At an Osborn's appartment, he discussed with Osborn about killing or not Spider-Man, saying that he was their greatest creation. An enraged Goblin attacked Octopus, and after a fight in the streets, Osborn ultimatelly killed Octavius, beating him to death.