Dennis ends up in the “genius” class after cheating on a placement test. There he meets a gloomy young man named Willard, who, after going home to Dennis's house, applies his brilliance to skateboarding, baseball---and breaking Mr. Wilson's window like a pro.
The Mitchells' car breaks down on their way to a camping trip. Enter Mr. Wilson, who, along with his wife, picks up the clan in his RV. A stinker of an ordeal soon follows when Dennis lets skunks into the RV before learning they have spotted fever.
Dennis is less than thrilled about dealing with several disruptions in his life, including Joey's crush on Margaret; Mr. Wilson's decision to move to a retirement community; and Dennis's mom's pursuit of a job in real estate, which leaves her no choice but to put her son in day care.
In the midst of waging a war against a neighborhood bully, Dennis accidentally captures a toothache-ridden Mr. Wilson. Later, both wind up on a wild adventure to the dentist's office, during which Dennis learns a lesson about the nature of bullying.
Dennis finds a fake shark and uses it to frighten his friends; Henry runs out of gas while driving Dennis and Joey through a safari; Henry takes Dennis to a horse track, and the little guy gets in the race.
Dennis accidentally brings a baby mountain lion home after mistaking it for a stray kitten; Dennis and Joey go to the circus with Mr. Wilson; Margaret helps Dennis and Tommy try to capture the Mudville swamp monster.
Dennis sells all of the Mitchells' possessions to raise money for charity; Dennis and Joey wreak havoc at a ski lodge until a snow beast appears; Dennis and PeeBee construct a robot to assist Dennis with cleaning.