Felonious Gru, a long-time supervillain, is deeply humiliated when a rival steals the Great Pyramid of Giza. Determined to regain his standing, Gru, his elderly assistant Dr. Nefario, and his Minions devise a plan to steal the Moon. To finance the heist, Gru seeks the help of Mr. Perkins, the director of the Bank of Evil, who demands that Gru first obtain a shrink ray. Gru and his Minions manage to acquire the shrink ray from a research facility, but it is stolen by Vector, a new supervillain who has also stolen the Pyramid.

In his attempt to retrieve the shrink ray from Vector’s heavily guarded fortress, Gru discovers that three orphan girls—Margo, Edith, and Agnes—are being admitted to sell cookies. Gru adopts the girls under the pretense of being a dentist, intending to use them as a distraction to reclaim the shrink ray. Although initially planning to abandon them, Gru finds himself bonding with the girls. When Gru is rejected by Perkins for the Moon heist, the girls and the Minions come together to fund the operation with their savings. Meanwhile, Vector’s father, Perkins, reprimands him for losing the shrink ray, but Vector remains confident in his ability to thwart Gru.

Gru successfully shrinks the Moon and prepares to return to Earth. However, his plans are disrupted when Vector kidnaps the girls, believing they are a distraction. Gru surrenders the Moon to Vector in exchange for the girls, but Vector refuses to return them. Fueled by anger, Gru storms Vector’s fortress, evading all of its defenses. Meanwhile, Dr. Nefario and the Minions discover that the effects of the shrink ray are temporary; as objects grow larger, they quickly revert to their original size.

Gru, with the help of Nefario and the Minions, rescues the girls just before the Moon enlarges and launches itself back into orbit. The Moon’s return causes Vector’s aircraft to be destroyed, leaving him stranded. Gru reclaims custody of the girls, and they all celebrate with a special ballet recital that turns into a joyful dance party.