But, as consequence to an accident at OsCorp, he was horribly injured, and was saved by Norman Osborn, who put him in an OsTech iron lung suit with four mechanical tentacles. Because his body has atrophied, Doc Ock cannot move, or even breathe without the high-tech Octo suit.
Otto hired the Frightful Four for a year to attack and collect data about Spider-Man. When the Trapster planted a tracking device on Spider-Man, the other three were able to locate him atMidtown High School and engaged him to provide combat data to Octavius. Otto contacted Norman, to ask him if he should order the Frightful Four to destroy the school to cover the witness problem, who become worried about his son, Harry, who was there.
After that, Otto ordered the Frightful Four to capture Spider-Man, and, when they failed, Norman warned Otto that failure will not be tolerated again.
Otto sent one of his creations, the Octobot, to get a bio sample from Spider-Man which he used to create the Venom Symbiote (an isolation of all the deadliest aspects of Spider-Man's DNA) which he intended to use as way to infuse the soldiers with Spider-Man powers, but he needed a few months to perfect it. Unfortunately, Osborn wanted it fast, and Otto winds up telling him he will have something for him in the night. However, the symbiote escaped. Otto's best guess was that the symbiote wanted to return to where it come from, Spider-Man. After the apparent destruction of the symbiote, Norman told him that it was a success and he want a new one that Spider-Man and his team can't destroy, Otto told him that he will make it his life work.
Why I Hate The Gym
Otto hired Taskmaster to infiltrate the school to learn who is and capture Spider-Man. When Taskmaster fails, he tricks Otto into believing that the school is a dead end for capturing Spider-Man so he can have his revenge. Otto becomes enraged and starts to destroy the lab.
Back in Black
When Harry used the small piece of Venom to become the new Spider-Man, Otto suspect that someone is using the Symbiote, but also noted that it is more focused and controlled, so he sends the Dragon Man robot to test the new Spider-Man. After the apparent defeat of Venom, Otto learns the truth about Harry being Venom, and hides it from Norman who is so fascinated by the power and savagery of Venom that he wants Venom, whatever it takes.
After Venom returns, he is seen talking with Osborn about getting Venom back. Norman hangs up on him when Harry enters the room. The former questions Otto if he knew about Harry being Venom. Otto denies it, asking "how could anyone know more about your son than you?". Believing him, Norman gives him a blood sample from Harry, and the scene ends with Otto saying he will give all his effort into seeing "what [he] can do with it".
The next time he is seen, he has already sent Whirlwind after Spider-Man, who, unfortunately, fails. Norman calls Octavius up while the latter is attempting to take notes from the fight. The former then precedes to berate him, as Spider-Man still has yet to be captured, and threatens to cut off the funding for his project. Unable to come up with anything else, Otto says he has a fail-safe plan-he'd go out and capture Spidey himself. Norman laughs at the idea, due to Octavius being a disabled shut-in, and gives him until sundown to catch Spider-Man. A bit later, he yanks Spider-Man off of a roller-coaster, much to the web-slinger's surprise, and introduces himself as "Doctor". In the ensuing fight, Spidey dubs him "Doctor Octopus"(much to his annoyance), and he makes references to Norman, but leaves his boss unnamed (much to Spidey's annoyance). During said fight, they wind up in a hall of mirrors, in which he finally knocks the web-head out. After arriving back at the lab, Otto calls Norman, showing his success. Their talk ends when Octavius hangs up on Osborn, deciding he's going to call the shots on what to do with Spider-Man, and when to do it. Inevitably, Spider-Man wakes up to having a blade whirring in his face. Using the blade, Spidey frees himself, and their rematch begins. In it, it's revealed Otto has been wearing an ear piece that allows Norman to continue talking to him, despite having gotten hung up on earlier, resulting in the former demanding that the latter "get out of my head! Stop tormenting me!". Spider-Man responds by telling Octavius to tell "him" to show himself. During the scuffle, Spider-Man attempts to contact Fury, as opposed to actually beating Otto first. He resorts to webbing the latter's "lung part" of his suit, causing him to collapse and gasp for air. This doesn't stop the doctor completely, though, as he resumes his attack on Spider-Man after Nick Fury has been contacted, and Norman has started the destruction of the place. When the place floods, Otto is unable to get himself to safety, and simply drifts further underwater. Spidey winds up saving him, but nearly drowns as a result. Back at SHIELD, it's revealed that the lab was too damaged for anything to be learned, and there was no trace of Otto when they arrived. However, they do have part of one of his tentacles, which Spider-Man had apparently holding onto "like [his] life depended on it". 
The Iron Octopus
Later on, Doctor Octopus (now using the name) sends an octo bot to hack Tony Stark's information. After the bot returns, Ock finishes his newest creation, an iron octopus suit. He precedes to attack Norman Osborn, and successfully sends Iron Man away for the entire fight. Instead, he easily smacks Spider-man and Nick Fury around, then takes off, taking Norman and Harry with him. Spider-Man shows up in his Iron Spider suit while the Doctor is trying to get Norman to beg him for mercy. Their rematch breaks out, during which Doc Ock attempts to tell Spidey that Norman behind the attacks as much as he was, but the web-slinger ignores him. He gets defeated by Spider-Man punching him through a few buildings, but his suit kept him from dying. Norman retrieves him some time later, and puts him into a healing tank, albeit, completely devoid of his tentacles, thus unable to move at all.
Following his fight with Iron Man, Doctor Octopus is shown to be in a tentacled orb when he manages to catch Spider-Man for Norman Osborn. 
Rise of the Goblin
Eventually, Doctor Octopus gets revenge by turning him into the Green Goblin and places a control collar on. Green Goblin. Green Goblin overcomes the control collar and attacks Doctor Octopus.
Doctor Octopus has returned to his previous appearance and sports some new glasses. He has been shown to be working on some serums that turns anyone that is injected into their system into human/animal hybrids. These serums have the DNA of lizards, vultures, scorpions, and rhinoceros. Dr. Curt Connors uses the lizard DNA to regrow his missing arm turning him into the Lizard.
Alex O'Hirn steals the rhino DNA and becomes the Rhino in order to get revenge on Flash Thompson for bulling him.
Doctor Octopus gathers Beetle, Electro, Kraven the Hunter, and Rhino to form the Sinister Six. To further his revenge and expand the Sinister Six, Doctor Octopus abducted Dr. Curt Connors and attached a control collar to him which mutated him into Lizard so that Lizard can be his sixth member. During the fight at the Statue of Liberty, Lizard broke free of the control collar and attacked Doctor Octopus. After Lizard escapes into the sewers, Spider-Man rips off Doctor Octopus' tentacles. Doctor Octopus and the remaining members of the Sinister Six are arrested by S.H.I.E.L.D.
Second Chance Hero
Spider-Man and Norman Osborn in the Iron Patriot Armor battle Octavius who uses a Octobot to project a holographic image of himself. He attacks them with Spider-Soldiers, super soldiers based on the Venom symbiote Octavius developed from Osborn's stolen research. Spidey and Norman together put an end to Octavius' plans, earning the Iron Patriot S.H.I.E.L.D's trust in the process.
Return of the Sinister Six
An armored Doctor Octopus and Lizard invades Ryker's Island and reassembles the Sinister Six by armoring up Electro, Kraven the Hunter, Rhino, and Scorpion. The Sinister Six give Spider-Man a hard time until Norman Osborn in the Iron Patriot armor and the rest of Spider-Man's team arrives. While Spider-Man fights Lizard, Iron Patriot fights Doctor Octopus while Spider-Man's team fight the other members of the Sinister Six. When the Sinister Six end up combining their attacks to take down Iron Patriot, Doctor Octopus plans to inject Spider-Man with the Goblin Serum. Doctor Octopus then injects Norman Osborn with the Goblin serum while Spider-Man restored Lizard to Dr. Curt Connors. Norman Osborn becomes Green Goblin where he defeats most of the Sinister Six. Though Spider-Man has won against the Sinister Six, Green Goblin gets away with the captive members of Spider-Man's team. After the Sinister Six were defeated, Dr. Curt Connors thanks Spider-Man for saving him.
Doctor Octopus returns and used Venom again and possessing bodies of Skaar, She-Hulk, Red Hulk and Hulk and later Venom was destroyed by Hulk and Spider-Man and Defeated to hands for the Agents of S.M.A.S.H.
- A file on Beetle's armor that could lead us to Doc Ock's secret location.
- Anti-Venom: Tell me, Doctor, how do you keep neural pathways stable while a symbiote's genetic code is being rewritten? Well! That question is not nearly as ignorant as I would have expected.Temperature serves as But why tell you my secrets? I work alone. I'm sure you've considered a ten-nanosecond intron pulse - rather than a steady stream? - Of course.That would induce a refractory phase in the cells and better absorb the energy.Jump.Go flat.It's responding to commands.Flip.Fight. This newly enhanced symbiote will finally bring about Spider-Man's downfall. Every symbiote needs a perfect bonding partner. The Anti-Venom can't be stopped or altered, only inhibited in a level 4 or 5 cadmium device with positive ion flow.
- Ock's Encryption