Takes the Awesome Android from Doc Connors' lab on the S.H.I.E.L.D. Helicarrier in brick form. It was found by Spider-Man for Peter and Luke to use in a science fair project. The creature started to grow and consume inorganic matter. They are able to reverse the process and return it to the lab.
Doc Connors was part of the S.H.I.E.L.D. group vacation in Peter Parker's imagination.
The Iron Octopus
When the Osborn's are taken to the Helicarrier for protection from Doctor Octopus, they are called into Doc Connors lab to view his discovery regarding a piece of the tentacle they recovered. Doc Connors explained that it was created by Dr. Otto Octavius a former colleague. Osborn reveals the Octavius was a former employee that died in accident. 
Rise of the Goblin
During Green Goblin's attack to the Helicarrier, Curt lost his right arm.
After S.H.I.E.L.D. raided one of Doctor Octopus' secret labs, Connors discovered a stash of mutagenic animal DNA Octavius planned to use to develop super-powered individuals, such as Venom and the Green Goblin. Dr. Connors planned to use this DNA for a different purpose - restoring human bodies. Namely, regrowing his own arm. Ignoring Spider-Man's warning about using it for such purposes, Connors took a serum of lizard DNA, growing back his lost arm. While it initially gave him great strength, Connors soon lost control of his mutation, transforming into a giant lizard creature. Spider-Man, with the help of his teammates and (surprisingly) Dr. Octopus, was able to put an end to the Lizard's rampage, transforming him back into Doctor Connors.
The DNA formula is used again to create the Rhino.
The Sinister Six
Doctor Octopus captures Dr. Curt Connors to lure Spider-Man to his underwater lab in the Hudson River. When Spider-Man arrives and encounters Doctor Octopus and his Sinister Six, Doctor Octopus activates a control collar on Connors to turn him into Lizard making him the sixth member of the Sinister Six. When Spider-Man corners Lizard who temporarily changes back, Doctor Octopus re-activates the control collar on Lizard who knocks out Spider-Man as the rest of the Sinister Six arrive. When Doctor Octopus states that they should have Spider-Man unmasked to complete his revenge, Kraven the Hunter suggests that Lizard should do the honors of unmasking Spider-Man. As Lizard prepares to unmask Spider-Man, Doctor Octopus controls Lizard to remove Spider-Man's mask as Kraven plans to do the job himself. Lizard attacks Kraven as Spider-Man tricks Rhino into flooding Doctor Octopus' lab. When Spider-Man has his team switch opponents during their fight at the Statue of Liberty, Spider-Man fights Doctor Octopus as Lizard breaks free from the control collar. Spider-Man then removes the control collar from Lizard. While Spider-Man's team watches over the other Sinister Six members until S.H.I.E.L.D. arrives, Lizard escapes into the sewers. As Lizard jumps off the sewer's waterfall, Spider-Man catches him with his webbing as he vows not to fail in restoring Lizard back to Connors. Lizard states that Spider-Man will keep failing as he cuts the web and falls into the water below.
Stan By Me
Stan the Janitor, Peter, MJ and Harry battle the Lizard who raided Midtown High to steal equipment from the school with Principal Phil Coulson in the process. Stan tells people to go for help which gives him time to put on his Spider-Man suit Lizard attacks Spider-Man in the dark only for Stan the Janitor to end up fending off Lizard. While in the boiling room, Spider-Man is attacked by Lizard and fights him until Lizard captures Harry Osborn as well when he got in the way of a tech panel. Spider-Man then enters the tunnels beneath Midtown High Schools to follow Lizard into the abandoned subway tunnels until Lizard floods the tunnel and makes off with Mary Jane Watson. Spider-Man and Stan the Janitor follow Lizard to the maintenance room where Lizard has assembled a machine with Harry Osborn and Phil Coulson tied up. The machine was created to stabilize his brainwaves, allowing to think clearly. While Spider-Man fought Lizard, Stan the Janitor rescued Mary Jane from flooding hole. Spider-Man tries to reason with Lizard until Mary Jane breaks free from him. While Stan the Janitor holds off Lizard, Spider-Man works on the machine which ends up driving the Lizard part of Dr. Connors out. Spider-Man fights Lizard until Stan the Janitor tells him to go on ahead while he holds off Lizard. Stan the Janitor takes out Lizard who manages to escape. 
Walter and Amanda Cage took over DocConnors Lab, but when talking with Spider-Man the Awesome Android accidentally frees Sandman who ends up stopping Awesome Android and putting out the fire Awesome Android caused. Sandman stated to Spider-Man that he just wanted to help. Nick Fury mentioned that he S.H.I.E.L.D. has been working to rehabilitate Sandman and hoping to make him a hero.
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.
- Voiced by Dee Bradley Baker