- “You don't give people hope, you take it away. Now, I'm going to take away yours.”
- ―Green Goblin[src]
Due to a recessive gene called 'Retroviral Hypodysplasia' passed on from his father, Harry quickly began to succumb to a disease that began to eat him away from the inside, starting with twitching in his fingers. After a failed attempt at obtaining some of Spider-Man's blood to try and cure himself, Harry injected a serum into his body made by Oscorp during their spider testing stages. Instead of it curing him, the serum simply quickened the process of his inherited disease and transformed his physical body as well as his mind, rendering him insane. As he struggled to move, he found a special. metallic suit, attached to a glider. Harry donned the suit, grabbed some explosives and flew the glider out of the building as the Green Goblin.
- “Peter Parker, it's like seeing a ghost.”
- ―Harry Osborn[src]
In 2014, the 20-year-old Harry returned home just before his dad passed away. Harry was now Oscorp's CEO and was soon reunited with his childhood friend. The two caught up, and Peter informed Harry about Gwen Stacy . Harry also became convinced that the blood of Spider-Man (whom he had figured out had gotten his powers from one of the now-destroyed spiders) would be able to cure him. Knowing that Peter had taken photos of the hero, Harry asked him to get in touch with Spider-Man. Later, Spider-Man appeared in Harry's home, but refused to give him his blood regardless of what Harry offered him, as he believed his blood would have a negative effect on Harry if it wasn't compatible.
Harry became increasingly desperate until his assistant informed him that Oscorp had drained venom from the spiders before destroying them. He tried to find out where it was stored, but came across information about Electro and was quickly locked out of the system. Donald Menken framed Harry to save himself, and had him fired. Enraged, Harry sought out Electro, who was at the time being held at Ravecroft, and freed him. Together with Electro, Harry headed back to Oscorp and took Menken hostage while sending Electro off to take out the city's power. Menken took Harry down into a secret area and was forced to inject Harry with the spider venom. The venom had a violent effect on Harry, seemingly accelerating the disease rather than curing it. In pain, he crawled over to an Oscorp prototype exo-skeleton suit and glider. Upon putting it on, the suit healed the damages done to his system.
Harry as the Goblin flew to the power plant on the glider, arriving shortly after Electro's defeat, the spider venom now seeming to be affecting his mind as well. Noticing Gwen with Spider-Man, he quickly realized that Spider-Man was Peter Parker. In a rage, Harry decided to destroy Peter's "hope": Gwen. Harry grabbed Gwen and flew away, with Peter giving chase. Shortly after, he threw her down into a clock tower, where Peter was able to catch her. Harry began fighting Spider-Man inside of the nearby clock tower, however Gwen was ultimately killed in the ensuing battle. Harry was knocked out and taken to Ravencroft, though Gwen's death caused Peter to give up the mantle of Spider-Man.
Months later, Harry was visited by Gustav Fiers, who informed Harry that he had found several suitable candidates for a project. Harry asked him to keep it small and sent him down to the secret area, to collect weapons and equipment for the chosen candidates. The first was Aleksei Sytsevich, who was given a rhino-like mech suit. Peter Parker re-emerged as Spider-Man shortly after to combat "The Rhino".
After "The Carnage Killer"'s massacre on the criminals, which led the first attack and war set in Oscorp between Russians and Shocker's gang, Harry was approached by Wilson Fisk the Kingpin for their cooperation to put an end of the crime war and would not allow a vigilante like Spider-Man to do so. On the other side of the conference, Harry was forced to make a deal with Kingpin, knowing he would take Oscorp away from him, Harry still refused the forceful kind of offer, even he had a same disease as his father. During a party at night with Fisk, he was targeted by a Russian's assassin whom disguised as a bartender to poison Harry to death, and luckily his best friend Peter secretly noticed about the bartender as he bump to him by "accident" to save Harry from being killed. Before transformed himself into Goblin shortly to cure himself from a disease, Spider-Man and Peter Parker tries to warned about the side effect of using Spider-Man's perfect cross-species blood without anytime in research would made him turned into a monster like Dr. Connor was as the Lizard, but Harry didn't listened to them and stating it would be waste of time as Harry will do on his own, he is foolishly using a spider-venom that turns him into Green Goblin. Unlike in the movie when his transformation into Goblin is nearly begin, Harry still remained as the head of Oscorp after learning that Oscorp had Richard Parker's spider-venom while asking the scientist for the serum he will use that results his transformation into Goblin, as well as overhearing from his employers that Kingpin does want to take over Oscorp and had a chance to finish him off as long as Harry lives as the head of the company. He is soon defeated by Spider-Man, whom later finds out Spider-Man its Peter and, asked Spider-Man to kill him because Harry doesn't want live in his mutated form. However, Spider-Man refused and telling Harry to think hard because there many people who are having a natural illness or same disease all over the world, even they don't have a money or resource has Harry's, and tells Harry if he didn't fight for himself, Harry will owe to them to find an answer for his mistake and do whatever he can make up for them. As Spider-Man leaves by telling a great man Spider-Man knew had taught him, and Harry tries to call back Spider-Man by his real name, Harry faints.
In the game version, Harry seems to be less-short temper, he does not meet Max Dillon yet, he's being threaten of dying by Menken replaced with Fisk in the beginning of some chapter before Task Force established, and seems not to be patiented in waiting for a bit research on Spider-Man's perfect cross species blood to cure him before Kingpin takes over Oscorp soon when he died. After transformation into Goblin, the scene does not involved Gwen Stacy as she still alive somewhere.
- Metamorphosis: Upon injecting himself with genetically modified spider venom, Harry transformed. The transformation changed Harry both physically and mentally. It turned his skin pale-greenish, made his hair stand up and gave him claw like fingernails. This transformation altered the chemistry in Harry's body, and possibly affected his brain, which could explain his apparent insanity and dehumanization, as well as making him more instinctual and homicidal. The transformation would have killed Harry, had he not put on the Oscorp Exo-Suit which healed him. The effects later wore off. Harry did, however, when asked if the effects had returned, say that, "It comes and goes".
- Superhuman strength: His strength of was enhanced by the exo-skeleton of Oscorp shown to be strong enough to be near or the same to Spider-Man. He was able to pin Spider-Man to the floor, though he took several hits while doing so and Spider-Man was weakened from his fight with Electro. He was even able to choke Spider-Man with one hand.
- Superhuman stamina: His stamina was very enhanced by the venom of the spider and the Oscorp exo-skeleton.
- Superhuman acrobactics: His agility was very enhanced by the spider venom. He was capable of making several quick maneuvers while on his glider and was able to seemingly leap several feet across a clock tower to tackle Peter to the floor when he was knocked off his glider.
- Superhuman speed: He appeared to be able to run faster than cars.
- Oscorp exo-skeleton: Harry wears a high-tech armor that enhanced his strength, speed and durability.
- Goblin Glider: An object made by Oscorp which is used for transport.
- Pumpkin Bombs: Grenades used as a weapon by the Green Goblin. The bombs are used as flying explosive grenades.
- Although credited as the Green Goblin, he isn't referred to that name in the film. However, at the climax of the film, when Gwen calls him "Harry", he claims that "Harry is dead!", thus giving way to the Green Goblin.
- In the The Amazing Spider-Man 2 game he is only referred to as the Goblin. However, when the subtitles are on, the game refers him as the Green Goblin.