At some point, Harry was born to Norman and was best friends with Peter Parker, he was Mary Jane's boyfriend until she left him. He swore revenge on Spider-Man after he saw him place Norman's corpse on his bed, thinking he killed his father. He then became the CEO of Oscorp.
When Harry funded Dr. Otto Octavius' fusion experiment, he provided him with the necessary materials, including tridium, which is one of the most powerful substances on planet Earth. After Octavius' appaling transformation into the frightening villain "Doc Ock", he sought out Harry one night at his manor. Ock made a deal with him in order to get more tridium. What Harry wanted in return: Spider-Man, alive. Octavius obliged, capturing Spider-Man and bringing him back to Harry. Osborn unmasked him to see who was really behind the mask, revealing Spider-Man's true identity of Peter Parker. Harry's only true friend was now his greatest enemy.
After having a halucination involving his father mentoring him about killing Spider-Man, he discovers his father's old lab, full of all of Green Goblin's war gear: masks, armor, weapons, everything he needed for revenge against Spider-Man. He undergoes the same transformation his father once did by injecting himself with the serum, enhancing every good and bad trait he ever had.
He then became the New Goblin, and sought after Peter at a performance of Mary Jane Watson's play. He attacks him with an array of high-tech weapons, but ultimately, Peter won the battle. After a high speed chase down a narrow alley, Harry falls and hits his head. Initially, Peter believes him dead, but he rushes him to the hospital, and he is saved. He does, however, suffer from serious memory loss, especially short-term. He doesn't remember the accident, his new identity as New Goblin, or Spider-Man's true identity.
Mary Jane asks Harry if she can come over when her relationship with Peter goes wrong. They end up kissing, something both of them regret immediately afterwards. Mary Jane quickly leaves, and Harry becomes very distraught. He begins drinking again, then he suddenly remembers everything he had forgotten, including Spider-Man's identity. He continues his plan of revenge on Peter, and tells Mary Jane to break up with him, just to hurt him. Mary Jane obliges after Harry threatens to hurt her, which makes her extremely heartbroken. Peter seeks out Harry at his estate, and they fight each other. After a long, brutal battle, Harry is defeated by an enraged and possessed Peter, who leaves him battered and bloodied.
Peter returns to Harry's estate to ask for his help after Mary Jane is held hostage by Venom and the Sandman. Peter claims that this isn't about them, but for her. Harry refuses, stating that Peter doesn't deserve his help. Peter, as Spider-Man, then leaves, and seeks out Mary Jane himself. Bernard, Harry's butler, approaches Harry with the truth about what happened the night his father died. He tells him that his father's wound was from his glider, and that Norman Osborn died by his own hands.
Harry, now believeing Peter when he said that he didn't kill his father, goes and helps Spider-Man defeat Venom and the Sandman as well as save Mary Jane. Spider-Man is tied by Venom and he is about to be impaled by Harry's glider, which is now under the control of Venom. Before the blade reaches him, however, Harry jumps in front and is impaled. Spider-Man manages to defeat Venom on his own, but is unable to save Harry. With both Peter and Mary Jane by his side, Harry died, much to the dismay of his old friends.