Gru, a supervillain, is disheartened when an unknown supervillain steals the Great Pyramid of Giza. Gru resolves to do better, with the assistance of his colleague Dr. Nefario and his Minions, by shrinking and stealing the Moon. As it would be costly to shrink and steal the moon, Gru seeks a loan from the Bank of Evil. Bank president Mr. Perkins is impressed by the plan, but will provide the money only if Gru can obtain the necessary shrink ray first.
Gru and the Minions steal the shrink ray from a secret base in East Asia, but the up-and-coming supervillain, Vector, who was also responsible for the Pyramid theft, immediately steals it from Gru. Gru attempts to break into Vector’s fortress to recover the shrink ray, but is defeated by numerous booby traps. However, he notices three orphan girls, Margo, Edith, and Agnes, who are able to easily walk into the base because they are selling cookies. Gru disguises himself and adopts the girls, planning on using them to infiltrate Vector’s base so he can get the shrink ray back. However, Gru has trouble nurturing them properly due to their rambunctiousness, their ballet classes, and his own ineptitude as a parent.
Eventually, Gru and the girls arrive at Vector’s fortress and Gru steals the shrink ray. The girls then suggest a day at a theme park; Gru agrees, believing he can abandon the girls there, but instead he warms up to them. Later, Gru contacts Mr. Perkins via video chat, stating that he finally has the shrink ray. Margo, Edith, and Agnes interrupt the meeting, and Perkins announces that he has lost confidence in Gru and will no longer fund his operations. As Gru tells the Minions he can no longer pay them for their services, the girls offer the contents of their piggy bank. Gru, inspired, sells parts of his lair to construct a spacecraft.