All of his life, Gru (voice of STEVE CARELL) has dreamt of being the world's greatest bad guy. Underneath his suburban home is a secret lair from which he, his army of worker-bee minions, and the mad scientist Dr. Nefario (voice of RUSSELL BRAND) hatch their latest plot: to shrink the moon and steal it from the sky.
Gru's arch rival, Vector (voice of JASON SEGEL), also plans to swipe the moon, and he appears to have what it takes to get the job done. He's already stolen the Pyramids of Egypt and replaced them with inflatable versions. His father, Mr. Perkins (voice of WILL ARNETT), is the president of the Bank of Evil and is willing to bankroll his dastardly deeds. Unlike Gru, he doesn't have a domineering mother (voice of JULIE ANDREWS) who never gives him credit for anything. And, now, he's got his hands on a super-secret shrinking ray that Gru covets.
All of Gru's attempts to get past Vector's heavy security to steal the shrink ray prove fruitless. Then, one day, he notices three orphan girls named Margo, Edith, and Agnes (voices of MIRANDA COSGROVE, DANA GAIER, and ELSIE FISHER) who easily gain entry by selling Vector some cookies. Gru immediately heads to the orphanage, run by the shrewish Miss Hattie (voice of KRISTEN WIIG), and adopts the three girls.
Soon, though, Gru finds that being a dad is just as hard as being a super-villain. Even worse, his growing affection for the girls begins to hamper his and Dr. Nefario's plans for the lunar heist. Eventually, Gru must make a choice.