Noah (Jonah Hill) is a college student who has been suspended and now lives with his mom. After a disagreement with her, he's lured into taking a babysitting job caring for the unruly kids of Mrs. Pedulla: the sexually confused Slater (Max Records), no-nonsense wild child Blithe (Landry Bender) and pyromaniac adoptee Rodrigo (Kevin Hernandez).
Soon Noah is invited to a party to have sex with his supposed girlfriend Marisa (Ari Graynor), who uses him only to get oral sex, and she agrees to have sex with him if he brings drugs to the party. Tempted by the offer, Noah steals Mrs. Pedulla's car and takes the kids to the city, where he meets Karl (Sam Rockwell) in his body-building shop. Karl likes to hide his cocaine in expensive dinosaur eggs and loves to make new friends. After getting drugs, Noah realizes that Rodrigo has stolen an egg from Karl; after a struggle, the egg bursts open, spilling all the drugs.
After he finds out the drugs are missing and calls Noah, Karl tells Noah that he has to come up with $10,000 or he will kill him. In a panic, Noah decides to take the kids back to their parents', but decides against it feeling he has to fix his own problems. He then takes the kids to the bat mitzvah party (to which Slater was invited) of a bratty popular girl who goes to school with Slater. There Slater sees his friend, Clayton (Alex Wolff), who lied to him earlier, saying that he couldn't hang out with him because his spider died. Clayton admits he lied because he was sick of hanging out with Slater at his house and not going anywhere, which hurt Slater's feelings.
Noah discovers the valet service has lost his van, which was actually stolen. Noah leaves, going to his father's house to see if he will give him the money he now owes Karl. When his dad berates him and refuses to give him money, Noah steals his father's car and breaks into his father's jewelry store, taking diamonds. Rodrigo, fascinated with bombs, puts a cherry bomb in the bathroom, blowing up the store. Noah, frustrated with Rodrigo's antics, yells at him and forces him to admit why he is so bad. Believing that no one in the family likes him, a frustrated Rodrigo throws all of Slater's meds out the window.
Slater has a panic attack in which Noah calms him down and acknowledges that he knows about Slater's homosexuality. Noah notices his stolen van and follows the thieves to a club where he runs across Jacolby (Method Man) and his girlfriend, who hates him because years ago Noah threw up in her grandmother's urn. Noah allows her to hit him as an apology, which she does, then makes amends. Noah runs into Roxanne (Kylie Bunbury), a girl he knew from college, and realizes she likes him.
Still on the run from Karl, Noah goes to the party to save Marisa, who is drunk and belligerent. When Karl shows up, Noah, Marisa, and the kids make a run from him, crashing into a park. With Noah about to die, Jacolby and his crew come and save him, beating Karl up while Noah runs and takes the kids back home. Marisa realizes that she was a terrible girlfriend and that she got Noah in all this mess. Noah agrees, letting her know that he is done risking everything for her when she doesn't really like him.
Finally Noah gets the kids home before their parents come back, cleaning up their mess. The kids all get extremely close to Noah and start to listen to him. Noah finally leaves after threatening Mr. Pedulla, acknowledging that he knows he is sleeping with his assistant, which Blithe had told him about. Roxanne meets him at the house, and they leave together, walking home hand in hand.