The family travels to Las Vegas when Hal experiences a dream about hitting the jackpot; Dewey and Reese enter an enormously obese rabbit in a contest; Lois gets to meet her favorite singer backstage; Otto and Francis get trapped in a well.
When an exhausted Lois falls asleep, Hal goes out for diapers, only to be branded a shoplifter; three beautiful girls use Malcolm, Reese, and Stevie to embarrass their prom dates; Dewey tells the baby a fantastic tale to keep him from crying.
Stevie goes into shock when he's told Kitty divorced Abe; Reese gets caught up in the hot-and-heavy entries in a diary, unaware it belongs to Lois; Otto and Francis have to put down an old horse; Dewey finds he likes the taste of baby food.
It's another family Thanksgiving, as Reese cons Hal and Dewey into helping him out with the cooking. Francis and Piama are also there, but they're not even speaking to each other. Lois tries to intervene, but it goes nowhere, as Hal prevents her from intervening. Soon after, all the family members start arguing with each other, claiming that this is the worst Thanksgiving ever. Meanwhile, Kirsten has invited Malcolm to her house party. He's having a blast without his family dragging him down and calls it the best Thanksgivng he's ever had in his life.
Malcolm's teacher forces him to secretly record Reese as he divulges his innermost secrets; Francis strikes back after a critic writes a scathing review about the hotel; Dewey starts his own novelty act at an outdoor mall; Hal's bosses are placed under arrest.
Lois gets Malcolm a job at the store, exposing Lois's well-kept secret; Hal and some other fathers start betting on babies; and sick of the way his brothers treat him, Dewey travels to the farm to visit Francis.
As Christmas approaches... a layoff at work prompts Hal to make money selling Christmas trees; Francis and Piama's peaceful holiday comes to a crashing end when Otto's German relatives show up at the ranch; and Lois tries to capture a squirrel that bit Craig.
Malcolm realizes the entire neighborhood has been throwing a block party when the family leaves town for an annual vacation; Hal and Lois participate in a kielbasa-eating contest; neighborhood kids pay money for a chance at beating up Reese; and Otto acquires a device for "extracting seed" from a bull.
When Malcolm becomes editor of the high school literary magazine, the principal instructs him to censor a well-written story; Lois encourages Hal to flirt with a new supervisor so he can keep his job; Francis teaches Otto how to waltz; and Reese pulls a prank on Dewey.
Grandma Ida makes another conjugal visit at the Wilkerson house. This time she isn't alone as she walks in with her beau, Mr.Li a wealthy, widowed Chinese man whom she met at a cruise. Hal and the boys see this as an opportunity to get Ida off their backs once and for all. But Lois thinks that her mother is up to no good as usual. Meanwhile, Malcolm has just got his tongue pierced, but it gets infected right away so he can't say any words that involves an "s" in them. On the day of his grandmother's wedding, he confirms his mother's suspicions when he finds ...
Malcolm volunteers for the company's softball team, only to realize that Lois is the coach; Francis sets out to prove he's not lazy; and Hal interviews for a job at a company that might be recruiting secret agents.
Lois' younger sister, Susan makes a surprise visit to the Wilkerson house. Immediately, she treats Malcolm, Reese and Dewey like the sons she wishes she had with Hal instead of being single and alone. She also treats Lois as a plague in her life and blames her for being unmarried status. She tells the boys that ever since she caught their mother having sex with their father, she has refused to accept their relationship. However, Susan is plagued with a kidney disease and Lois tries to offer hers for her sister.
Lois has a dispute with Hal and the boys' favorite restaurant; Malcolm clicks with his girlfriend's family... to the point where he forgets about his girlfriend; and Francis gets an assistant who tends to his every whim.
Reese storms out and gets his own apartment. Francis uses the opportunity to blame Lois for all the issues in the family and Malcolm is forced to coach a jock who gets every free break in the world. The new found independence for Reese leads to an unheard of 'A', but, naturally reality comes home to bite with his novel approach to clean clothes.
Lois accompanies Malcolm to his first college visit, where she clashes with a resident advisor; Reese pretends he's a drug user to woo a pretty narcotics officer; Francis and Otto open their own childcare center; and Dewey constructs his own musical instrument.
Reese inadvertently perfects Malcolm and Stevie's science experiment, but can't remember how he did it; Dewey dreams up reasons for people to buy the candy he's selling door-to-door; and Francis aids a piglet.
Lois has just found out that she has a half-sister named Roberta and brings Reese, Jamie and Malcolm with her to meet their aunt and cousins. Her step-mother, Sylvia comments that she looks exactly like Victor and gives her a warm welcome. Despite some nervous moments between them, they're getting along great. Lois thinks it's going to be nice, quality time with them until a furious and vengeful, Ida arrives at the house to spoil everything. She has lost the court case and demands for Victor's pension from his secret family. Meanwhile Hal and Dewey plan to go racing ...