Headmaster Sturgeon has had enough. In an attempt to put an end to Bruno and Boots high jinks, he declares that they are to be separated; no shared classes and, most certainly, no shared dorm room. This punishment is worse than anything the boys could have imagined. However, if Bruno and Boots can alienate every boy in Dormitory 3, Sturgeon will be forced to re-unite them. The plot almost succeeds, but one misstep forces the girls from the Scrimmage Academy for Education and Awakening to move into Macdonald Hall, leaving Bruno and Boots back where they started.

Based on The Bestselling MacDonald Hall Book Series by Gordon Korman. Bruno Walton and Melvin "Boots" O'Neal are the most infamous troublemakers at MacDonald Hall - a supposedly prestigious school for boys. Bruno, the brains behind the operation, has managed without fail to convince Boots to tag along on his countless prank operations whether it includes stealing a rival school's mascot, switching the school's flag or invading Miss Scrimmage's Academy for Girls Education and Awakening across the road. Despite their ongoing pranks, Bruno and Boots LOVE their school and are willing to do anything to protect it.

The Board of Directors launch an experimental educational program, introducing authoritarian Assistant Headmaster Mr. Wizzle to the boys of Macdonald Hall and the miserable Assistant Headmistress Ms. Peabody to whip the girls of the Scrimmage Academy into shape. With new dress codes, psychological testing, and early-morning wake-up calls with track laps as punishment, the boys and girls decide Wizzle and Peabody have to go. But how? As they pull out all the stops, they ultimately turn to the theory that “love conquers all” to oust the pair once and for all.

To celebrate Ms. O's 100th anniversary, the agents go back in time to witness her last case as an agent. However, something goes wrong and they change the future for the worse.