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Once on Earth, he was raised by imprisoned criminals in Metro City and was socially excluded on school, starting an early rivalry with the increasingly popular Metro Man. He would later go on to become a super villain, believing that to be his life's vocation, and eventually succeeded in defeating his nemesis and taking control of the city as its self-appointed ruler.
As a villain, he takes great enjoyment in fighting his nemesis and tends to have a playful view on hero/villain combats, even referring to them as a game and stating some of the generally accepted rules. Like most supervillains, he is known to use a secret lair and is helped by the loyal Minion and an army of sentient aggressive robots. He also appears to have some sort of speech impediment, as he commonly mispronounces several simple words.
In the beginning of the film, Megamind and Minion (as infants) are sent away in a space pod to escape a black hole threatening their home planet by Megamind's parents. During the journey to Earth, another space pod flies by, with a baby Metro Man, who is also sent away to escape from the black hole threatening his home planet. Both pods land into Metro City, but results vary: while Metro Man's pod lands near a living couple who begin raising him as their own son, Megamind's pod lands near the Metro City prison, where the prisoners raise him. The prisoners teach little Megamind all about right and wrong using "Baby Supervillains" CD's, DVDs, and cards. During their childhood life, Metro Man is popular among the kids while Megamind is ridiculed, which would explain why Megamind becomes the villain and rival to Metro Man. The feud between Megamind and Metro Man remains constant until one day Megamind kidnaps news reporter Roxanne Ritchi and lures Metro Man into a trap near an observatory, where Metro Man becomes weakened by the copper lining inside the observatory before Megamind's death ray destroys the observatory, leaving nothing for Metro Man to be left as a skeleton with his cape. Upon witnessing this, Megamind revels in victory against Metro Man and takes over Metro City to himself. Though at first, Megamind feels good of his victory, later on he feels isolated and depressed, as he finds his villainy with no meaning without anyone to stop him. While attempting to destroy the museum dedicated to Metro Man, Megamind disguises himself as its curator Bernard to prevent Roxanne from finding him. It is then that Roxanne made a comment that inspired the disguised Megamind to create a new superhero to battle against him. Deciding to keep things back in balance again for the good of Metro City, Megamind creates a serum containing Metro's Man powers, coming from Metro Man's DNA found in his old cape. He intends to inject the serum to a person worthy enough to defeat him and continue the greater good. Just before he could do so, Roxanne sneaks into his lair with her cameraman Hal Stewart, intending to find out what Megamind's plans are. The resulting chaos ended up with the serum accidentally injected into Hal, who would later inherit all of Metro Man's powers. Taking the opportunity, Megamind heads onward to Hal's apartment, disguises himself as Hal's "Space-Dad", training him to become a hero for days. During the training, Megamind gives Hal his superhero name, Titan, to which Hal misinterprets as 'Tighten'. At the same time, Megamind develops a relationship with Roxanne under his Bernard disguise. Unfortunately, unknown to Megamind, Hal himself also has feelings for Roxanne, intending to use his own powers to win her heart for himself, as he believes that being a hero means to get the girl for himself rather than doing the greater good. As Megamind continues his date, he starts to lose interest in villainy, causing Minion to leave him after a fallout, feeling somewhat betrayed. Later on a dinner date, Megamind's Bernard disguise falters away, leaving Roxanne to dump him, leaving him to forget where he left his invisible car that contains the same defuser gun that injected the powers to Hal. Deciding to continue with his plan, Megamind waits for Titan to arrive him, only to seek him out again in his apartment. It was then Megamind discover that Titan has decided to use his powers for nefarious purposes, as it was evident of Titan having stolen lots of money. It was then Megamind realized that Titan's decision to become a villain resulted from Roxanne dumping Titan after a certain mishap came between the two while she was dating Megamind under his Bernard disguise, who Titan felt jealous against. During the tide, Titan decides to establish a partnership with Megamind, but Megamind, outraged to seeing his 'hero' turning out to be a selfish jerk, refuses, and instead goads Titan to fight him by revealing his 'Space-Dad' and 'Bernard' disguises. As planned, Titan fights against Megamind, unleashing his rage against him, and finally manages to defeat him, berating him for 'stealing' Roxanne. Megamind initially congratulates Titan for his victory and awaits to go back to jail again, but later finds out that Titan wants to kill him instead of turning him over to the authorities. Shocked, Megamind orders his Brain-Bots to initiate a backup plan: to contain Titan in a copper-based sphere. This fails, however, forcing Megamind to flee while Titan himself start to terrorize Metro City as its new villain, causing more damage to the city than Megamind has ever done. Confused about the inconsistency of the copper as a weakness, Megamind turns over to Roxanne, apologizing to her for his actions on her and convincing her to find Metro Man's old lair, which they manage to track down. They are surprised to see that Metro Man is actually alive, demanding an explanation for what happened. Feeling somewhat remorseful, Metro Man explains to Megamind and Roxanne that he felt tired battling against Megamind, as he feels that Megamind is having emotions during their feud. Metro Man also explained that, like Megamind, he never made a choice to decide what he wants to be in life despite his success as a superhero, and decides to retire by faking his death to pursue a career as a musician. Megamind understands Metro Man's intentions, but pleads to him to stop Titan, to which Metro Man respectfully refuses, knowing it would be against his vow to be making a choice in life. Eventually, Metro Man encourages Megamind to stand up for the greater good and fight back against Titan, to which Megamind refuses, stating that he will always be the failing villain to be. Having no more leads to stop Titan, Megamind decides to turn himself back to prison, intending to pay the price for his actions. With the supers no longer helping, Roxanne calls to Titan, trying to appease to his conscience, but Titan retorts that by denying that he has got any good in him, and instead kidnaps Roxanne and tying her up in the top of Metro Tower, intending to goad Megamind out to fight him by threatening Roxanne's life. Seeing this on TV, Megamind pleads the Warden to release him, even going so far to apologize and pay for the mistakes he done in the past (including hurting his dear best friend Minion). In an act of surprise, Minion disguises himself as the Warden, accepting Megamind's apology, and the two head off to stop Titan in his tracks, while the real Warden (who is tied up by Minion to help Megamind) wishes them good luck. Megamind and Minion arranged a plan of rescue and action, by having the latter to disguise himself as the former to save Roxanne with the help of the Brain-Bots, as well as the former to disguise himself as Metro Man to track down Titan and verbally berate him for his actions. The plan somehow worked, although Minion ended up being stabbed by the tower's rod near a water fountain by Titan, while Megamind, under his Metro Man disguise, orders Titan to leave Metro City and never return. Titan agrees to go, but later returns after realizing that the 'hero' said the word 'metrosity', something which only Megamind says, as he has trouble saying some of the simple words, such as 'hello' for 'ollo'. Seeing that it didn't work, Megamind continues fighting against Titan to no avail, that is until Roxanne discovers where Megamind left his invisible car and his defuser gun the night she dumped him. She explains this to Megamind, leaving him to finally get hold of the defuser gun. Just as things are about to go down when Titan decides to finish off Roxanne near the water fountain, Megamind dehydrates himself into a cube, landing into the water, where he re-hydrates himself and uses the defuser gun to remove all of Titan's powers for good. Having defeated Hal for good, Megamind goes in to save Minion by throwing him into the fountain water, since fish need water to survive, thanking him for his help. It was then the citizens of Metro City cheered for Megamind as their new hero. Feeling good about this, Megamind realizes that destiny itself is the path he can choose for himself. Feeling capable to becoming a real hero, Megamind arranges the Brain-Bots to repair the damage he and Hal has done to Metro City as retribution, and the Metro Man museum gets dedicated to him. As for Hal, he gets arrested and thrown into Megamind's old cell as punishment for his actions. During a celebration of Megamind as the new hero, a disguised Metro Man within the audience silently gives his congratulations to Megamind, having known that he had some good left in him. To make things better, Roxanne develops her relationship with Megamind in honor of his actions for her. The film ends with Megamind, Roxanne, Minion, and everyone in Metro City dancing to the tune of Michael Jackson's "Bad".