Mac (Seth Rogen) and Kelly Radner (Rose Byrne), a young couple navigating the challenges of new parenthood with their baby daughter, Stella, find their previous lifestyle slipping away. Their situation strains their relationship with friends Jimmy Blevins and his ex-wife, Paula. Suddenly, they discover that the notorious Delta Psi Beta fraternity has moved in next door, led by its charismatic leaders, Teddy Sanders (Zac Efron) and Pete Regazolli.
This fraternity is determined to make their mark by throwing an unforgettable end-of-the-year party that could earn them a spot in Delta Psi's Hall of Fame. Initially, when Mac and Kelly confront Teddy about the noise, he readily agrees to help—on the condition that they reach out to him first instead of the police. To win them over, Teddy extends an invitation to their party, where Kelly meets his girlfriend, Brooke Shy, while Mac is shown Teddy's impressive stash of fireworks and their electrical breaker box.
However, as the noise persists and their attempts to reason with Teddy fail, they resort to calling the police. This backfires when Officer Watkins reveals their identity to Teddy, leading to a series of hazing events from Delta Psi. Realizing they are stuck in a three-strike policy, the couple seeks help from the college dean, Carol Gladstone (Lisa Kudrow), only to discover the fraternity has already used one of its strikes.
In a bid to sabotage Delta Psi, Mac damages their house, intentionally flooding the basement, prompting the fraternity to resort to absurd solutions like selling embarrassing photos to raise money for repairs. As tensions rise, Kelly devises a plan involving Pete and Brooke, leading to chaotic confrontations that escalate the rivalry between both parties.
Desperate for victory, Mac and Kelly hire a pledge to gather evidence against Teddy but are met with unexpected kindness from him. Frustrated, Teddy retaliates with a series of pranks aimed at the couple. Seeking revenge, they attempt to deceive Teddy with a counterfeit letter allowing parties and plan to catch him unaware, culminating in a wild party filled with chaos.
As the story unfolds, Mac and Kelly's ultimate showdowns with Teddy result in explosive confrontations, a comical series of antics, and unexpected twists—including a dramatic revelation that leads to Teddy taking the blame. After the dust settles, Mac and Kelly return home to embrace their roles as loving parents, adjusting to their newfound family life.
Months later, Mac has a chance encounter with Teddy, who is now finding his footing as a shirtless greeter at Abercrombie & Fitch. Their warm exchange shows how far they've come, and the story concludes with the couple joyfully taking photos of Stella dressed in cute outfits while declining an invitation to a wild party, fully accepting their roles as parents.
