After Megamind has taken over the town, his large "No you can't" posters are a reference to President Barack Obama's 2008 campaign posters featuring the slogan "Yes we can".

The film's plot was based on the premise: "What if Lex Luthor defeated Superman?"

Ben Stiller and Robert Downey, Jr. were approached for the role of Megamind, but turned it down due to scheduling conflicts. Stiller, however, appears in the role as Bernard the curator.

To promote the film, Will Ferrell assembled 1,580 of his friends and their acquaintances at a superhero costume function. This party set a Guinness World Record for the largest gathering of superheroes.

There are numerous references to Superman in this film: The way Megamind's parents put him in a capsule to Earth just before his planet is destroyed. The love interest is a reporter. Hal's "space dad" is modelled after Marlon Brando, as Superman (1978)'s father in Richard Donner's film version. Almost all of Metro Man's super powers are the same as Superman's. Megamind's pronunciation of Metro City has the same stress pattern as 'Metropolis" in Superman. Megamind takes on a bespectacled secret identity similar to Clark Kent. In the Metro Man Museum, there's a statue of Metro Man preparing to catch an airplane. This is a reference to John Byrne's Superman comics, where Superman made his first appearance by catching a plane and saving Lois Lane.

Megamind's dehydration gun also bears the commands DECOMPRESS, DEBILITATE, DEMORALIZE, DECOUPAGE, DEREGULATE, DEATH RAY, and DESTROY.

Megamind mispronounces words twenty times throughout the movie, most noticeably Metro City as "Metrocity" (rhyming with atrocity).

Metro City is located in Michigan. This can be clearly seen in a shot where Megamind's satellite is in orbit around the Earth.

Guillermo del Toro was hired as a creative consultant three weeks before the film completed production. He majorly assisted in editing the film to make it more exciting.

Megamind's invisible car is a combination of two famous superhero vehicles: the Batmobile and Wonder Woman's invisible plane.

Hal Stewart is named after two characters who have held the title of the Green Lantern, Hal Jordan and John Stewart.

The film was originally titled "Master Mind". However, the name had already been trademarked by the makers of the 1970s board game and television show Mastermind (1972), so it could not be used. It was then going to be titled "Oobermind", which was a misspelling of the term "über-mind." The word "über" refers to something that is large or great; in this case, the title character's over-swollen skull/brain. But it didn't sound right, so it was revised to become "Megamind".

David Cross was based in London during production, so his performance was literally phoned in.

Massachusetts Branch Showcase Cinema accidentally showed Saw 3D: The Final Chapter (2010) instead of Megamind at the time of Megamind 's release, frightening young audiences.

Instead of voicing his character from within a sound booth, Brad Pitt, who is a very active actor, insisted on using a handheld microphone for his performance and roaming around the studio.

This was originally pitched as a live-action film.

Brad Pitt's first voice acting job since Sinbad: Legend of the Seven Seas (2003), another DreamWorks film.

Each of the three superhumans in the film has a unique color scheme: Megamind's prominent color is blue, Metro Man is always seen with white, and Titan is colored red.

When Megamind (Will Ferrell) is channel surfing towards the end of the movie, he comes upon a news report of a squirrel water skiing. Ferrell had played Ron Burgundy in Anchorman: The Legend of Ron Burgundy (2004), in which Burgundy does a report on a water skiing squirrel.

Some of the words on Hal's t-shirts include "Game Over" and "Error 404: Request Not Found".

In the last dance scene during "Bad", Megamind does the Dougie, the Stanky Leg, and the Jerk.

Will Ferrell and Tina Fey's biggest grossing film.

There are a total of sixteen face smashes throughout the movie.

According to Director Tom McGrath, the film drew inspiration from Batman: The Movie (1966) and Superman (1978).

Megamind and Metro Man's styles are based on Alice Cooper and Elvis Presley.

The observatory was modelled after the Griffith Observatory outside Hollywood.

A whole crew of animators was dedicated solely to the movement of capes.

This movie was promoted at the 2010 San Diego Comic-Con International, with Tom McGrath, Tina Fey, Jonah Hill, and Will Ferrell, who was dressed as Megamind.

Despite a worldwide gross in excess of three hundred twenty million dollars, this is one of DreamWorks Animation's lowest grossing films.

Megamind plays a snippet of Minnie Ripperton's "Loving You" after supposedly killing Metro Man and taking over Metro City. Will Ferrell, the voice of Megamind, was castmates on Saturday Night Live (1975) with Ripperton's daughter, Maya Rudolph.

One of the venues, on which Megamind trains Hal to be Titan, is the same venue used in Donkey Kong, complete with rolling barrels and angled surfaces.

When Megamind trains Hal, he uses a training regimen based on Hal's love of video games. This is similar to Kung Fu Panda (2008), where Po was trained through food-based exercises.

The film's Japanese release was cancelled, following the devastating 2011 earthquake and tsunami.

Is the only DreamWorks Animation film directed by Tom McGrath to not become a franchise.

The least expensive Dreamworks Animation film released in 2010, only costing $130 million to make when compared to the $165 million it cost to make How to Train Your Dragon (2010) and Shrek Forever After (2010).

The second collaboration between Will Ferrell and David Cross. The first was Curious George (2006), which was also animated.

Third DreamWorks Animation film for Ben Stiller, after Madagascar (2005) and Madagascar: Escape 2 Africa (2008), which also had been directed by Tom McGrath.

The idea that Megamind chose the name "Titan" for Hal's alter ego, because it was the only name he could trademark is amusing, but not factual. There have been several superheroes named "Titan". Most notably, by Dark Horse comics beginning in 1993.

This is David Cross' second DreamWorks Animation film after Kung Fu Panda (2008).

The seventh best selling DVD of 2011.

Just under one hundred thousand storyboards were created for the film.

Minion while analysing Hal after he gets given super powers states that he's 28 year old, which is one year younger than his voice actor Jonah Hill had been at the time of this film's release.

Jonah Hill's 2nd animated film of 2010, after How to Train Your Dragon (2010) which was also from Dreamworks Animation.

Second DreamWorks Animation film where "Little Less Conversation" by Elvis Presley is played at some point in the film, after Shark Tale (2004).

J.K Simmons voices the character of the warden but in HBO's Oz, he plays a white supremacist prison inmate by the name of Vernon (Vern) Schillinger.

Ella Olivia Stiller, Quinn Dempsey Stiller: Producer Ben Stiller's children are the children in Megamind's childhood.

Justin Theroux: Script consultant as Megamind's father.

In the early portion of the movie, when Megamind has Metro Man trapped in the real abandoned observatory, look closely at the scene where the images of Megamind and Metro Man are being projected upon the buildings. Just after Megamind orders Minion to fire the death beam, there is a single frame where Metro Man fades slightly from the observatory screen and reappears faintly behind Megamind on the opposite screen. This foreshadowed Metro Man faking his death through superspeed.

When Metro Man is discovered, Megamind at first believes he is a ghost and says "Speak, apparition". This line came from William Shakespeare's Hamlet, Act V, Scene 1.

The dresses Roxanne wears throughout the film visualize her relationship with Megamind. When she first appears, she wears a red dress, when Megamind was her enemy (blue is the opposite of red). Later, she wears purple, as she and Megamind develop a better relationship. Roxanne's final dress is blue, as she has fully accepted Megamind.

When Metro Man faked his own death by escaping in the last millisecond, and replacing his body with a skeleton, it directly mimics events in the major DC Comics storyline "52", which documents a full year where Superman, Batman, and Wonder Woman have disappeared from the public eye and are presumed dead (similar to the events of "Megamind"). In "52", time-travelling superhero Booster Gold also faked his own death in an identical fashion to Metro Man by replacing his body with a skeleton at the last second.

During the opening of the Metro Man museum, "A Little Less Conversation" by Elvis Presley plays. This foreshadows the later part of the film, when it is revealed that Metro Man faked his own death, grew a beard, and lives in hiding, as persistent rumors claim Elvis did.

Hal the cameraman is seen wearing a yellow "sad face" badge. This is a tribute to the Alan Moore comic "Watchmen", where The Comedian wore a yellow "smiley face" badge. Since The Comedian was an unbalanced vigilante, this foreshadows Hal's instability and corruption.

Megamind brings yellow roses to Metro Man's statue after Metro Man's apparent death, yellow roses are symbolic of friendship.

At the end, when Michael Jackson's track "Bad" was playing, and Hal was dancing along it, the Warden was seen to play along with two of his guards. Their "head shaking step" was taken from Saturday Night Live (1975)'s "what is love" skit, which also starred Will Ferrell.

Megamind lands in a prison, where he is raised to be a criminal. This alludes to "Superman: Red Son", a graphic novel which demonstrates what could have happened if the infant Superman had crash-landed, and was raised in the Soviet Union. Both also have similar endings: the hero retires by pretending to be dead, goes into hiding, and leaves his work in the hands of his former nemesis.

Minion's suits increase in scale throughout the film: he is first seen wearing a remote-controlled suit in Megamind's childhood. He is seen throughout the film in his own robotic suit. At the end of the film, he is riding the giant battle suit.

In the office, where Megamind in lamenting his destruction of Metro Man, the camera pans across the room until it stops on Megamind addressing an infamous "Drinking Bird". As the camera pans, you can see what appears to be the Ark of the Covenant from Raiders of the Lost Ark (1981) as well as what seems to be the title statue from The Maltese Falcon (1941) on the desk to the right of Megamind, as he begins to address the Drinking Bird.

Hal Stewart's appearance was based on Superman's friend and photographer Jimmy Olsen, and his character was based on Spider-Man's rival and photographer Eddie Brock.

At school, the young Megamind dehydrates Minion. When re-hydrated, Minion is floating upside down, pretending he is dead, foreshadowing faking his demise later in the movie. In the same scene, Metro Man is playing "Itsy Bitsy Spider" on the guitar in the background, also foreshadowing becoming "Music Man".

After Megamind and Roxanne Richie discover Metro Man in hiding, he sings a snippet of a song for them. The lyrics being, "I have eyes that can see right through lead". The tune which he sings it to is Nirvana''s 1991 song "Come As You Are". Appropriately, lead is the one thing that Superman cannot see through.

During the climax, Minion (David Cross) is able to let Megamind (Will Ferrell) out of prison to face off Titan (Jonah Hill) and become a hero, in disguise as the prison warden (J.K. Simmons) after apologizing for his villainry. Cross and Simmons appeared in DreamWorks Animation's Kung Fu Panda 3 (2016).