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The latest film of the franchise takes in an estimated $125.1 million on its first weekend and outdoes its predecessor 'Harry Potter and the Goblet of Fire'.
The family animation earns about $7 million more than the newcomer which draws a fair number of female audience.
On their debut weekend, the DreamWorks animation and Robert Downey Jr.-starring comedy sit on the first and second spots respectively, followed by 'Colored Girls'.
The two voice cast were joined by producer Ben Stiller at the Wednesday event which took place at the AMC Lincoln Square Theater.
Held one day before Halloween, the premiere sees the reincarnation of Batman and other fictional characters in the guests which included Will Ferrell and Justin Bieber.
In one of the featurettes debuted to highlight the film's characters, Brad Pitt's Metro Man looks unkempt as he decides to succumb to his inner passion as a musician.
The movie will start out with a look at Megamind who is sent down to Earth and how he ends up living among criminals and deciding that being a super villain is his destiny.
Thousand of people came in various superhero costumes at the gathering in Los Angeles which broke the Guinness Book of World Record.
The third trailer released for the 3D animation explains how Megamind's arrival on Earth to become a villain takes a U-turn.
Will Ferrell, who dresses as Megamind, and Tina Fey unveil a five-minute footage from the animation, while Sylvester Stallone brings his male co-stars to show a clip from the action movie.
The likes of 'Megamind', 'Tron Legacy', 'Salt' and 'The Expendables' will fill the first day of the convention this year with the cast and footage promised for the panels.
In addition to the final installment of the franchise, 'Harry Potter and the Deathly Hallows', the studio lines up 'Green Lantern' and 'Sucker Punch' for the upcoming convention in San Diego.