When a busload of tourists stops at the Great Pyramid of Giza in Egypt, a boy named Justin accidentally falls onto it to discover that it has been stolen and replaced by an inflatable rubber duplicate. News of the theft shocks and puzzles the world.
In the middle of a suburban neighborhood sits a black house with a dead lawn. Unbeknownst to the neighbors, hidden deep beneath this home is the vast secret hideout of the supervillai…n Gru (Steve Carell) and his army of “minions,” which are tiny yellow pill-shaped humanoids in overalls and goggles. When he learns of the Pyramid theft, his pride is badly wounded and he resolves to pull the biggest heist in world history: stealing the Moon. Gru tries to get a loan from the local Bank of Evil (formerly Lehman Brothers), where he meets a young supervillain named Vector (Jason Segel). While Gru is reading through the blueprints for his Moon heist rocket, Vector annoys him by talking about his name and showing him his newest weapon, a gun that shoots piranhas. Mr. Perkins (Will Arnett), the bank president, refuses to give Gru a loan until he obtains the shrink ray necessary for the plan. He tells Gru that he is getting too old, and the new supervillains are younger with more money-producing schemes – like Vector, who is revealed to be the one who stole the pyramid. As Gru leaves the bank, he shoots Vector in the head with his freeze ray while he is trying to reload his piranha gun.
Gru and his minions steal the shrink ray from a secret lab in East Asia, but Vector promptly steals it from him and shrinks his ship as revenge for freezing his head; Gru attempts to get it back, but all his attempts to enter the base prove futile. After seeing three orphaned girls named Margo (Miranda Cosgrove), Edith (Dana Gaier), and Agnes (Elsie Fisher) get into Vector’s lair to sell cookies, Gru adopts them in order to use them to steal back the shrink ray. Vector has placed a large cookie order, so Gru has his assistant, Dr. Nefario (Russell Brand), build several cookie-shaped robots to slip into the boxes. The cookie robots are designed to infiltrate Vector’s lair from the inside and help steal the shrink ray from Vector’s vault. The theft nearly fails when the robots inadvertently seal Gru inside the vault, but he and his minions eventually (after a close call) escape through the main entrance.
On the way home, the girls ask to go to an amusement park called Super Silly Fun Land; Gru agrees to take them, intending to leave the girls there, but is forced to ride the roller coaster with them, and bonds with them during the trip. Back at home, he fine-tunes his plan and presents it to Mr. Perkins while being interrupted by the girls. Perkins surprises him by again refusing him the loan–claiming that while he doesn’t have a problem with the plan, he doesn’t want Gru to do it. This leads Gru into a flashback of his childhood, where we see he’s wanted to go to the moon ever since he was a child. He tried to impress his mother (Julie Andrews) with models (and an actual working model) and make her proud of him, but she never seemed to care about anything he did-thus fueling his desire. Perkins then tells Vector (revealed to be his son Victor, who named himself after the mathematical term) that Gru has the shrink ray. Though Gru is ready to abandon his plan due to lack of funds, the girls and the minions take up a collection to keep it going.
After a month or so passes, Nefario, beginning to see the girls as a distraction to Gru, contacts Miss Hattie (Kristen Wiig), the girls’ nasty mistress from the local orphanage, who arrives to take the girls back to the orphanage after he claims Gru wanted to give them back. Both Gru and the girls are heartbroken. The moon heist and an important ballet recital the girls are in fall on the same day. With a broken heart, Gru flies off to the moon.
Gru shrinks the Moon, pockets it, and rushes back to Earth when he finds the recital ticket (originally given to him by Agnes and slipped into his pocket by one of the minions prior to the launch) and realizes he has time to catch it. However, it has ended by the time he arrives. On the seat that the girls reserved for him, he finds a note from Vector, who has kidnapped the girls, telling him to bring the moon. After forcing Gru to hand over the moon, Vector goes back on the deal and keeps the girls as his captives. This enrages Gru, who storms Vector’s lair, his defenses proving useless. Vector then leaves his lair in an escape pod with the girls inside. Gru chases after them, attempting to hitchhike on the exterior of the ship, and nearly falls to his death, but is rescued by Dr. Nefario in the ship that Vector shrank. Nefario reveals that the effects of the shrink ray are not permanent and the effect wears off at a rate proportional to its original mass (which he calls the “Nefario Principle”). As Gru gives chase to Vector, the effects of the shrink ray on the Moon begin to wear off, causing the Moon to grow and smash open the glass bubble holding the girls. Gru rescues them with the help of his minions, while the (rapidly-expanding) Moon wrecks Vector’s controls, causing his ship to hyperjump and carry the moon back into orbit.
Gru and the girls settle down to live a happy life as a family, while Vector is stranded on the Moon with a minion that drank a sample of anti-gravity serum and floated out of the lab after Nefario forgot to close the skylight. The girls give a special recital for the minions, Gru, and his mother, who, after years of neglecting her son, finally tells him she is proud of him. The music changes from Swan Lake to disco, and everyone present rushes onstage to dance.