As Greg's parents prepare for a weekend escape, taking along Manny, his older brother Rodrick sees the chance to throw a party without supervision. He ropes Greg into helping, but rather than contributing, they end up shouldering all the responsibilities while Rodrick lounges back, grinning mischievously. In a clever move to gain leverage over their host, Greg tricks Rodrick by loosening the doorknob and capturing scattered evidence on his camera, using it as blackmail to force Rodrick into compliance.
The next day, as they await their parents' imminent return, Rowley bolts from the house, leaving Greg to confront Rodrick about his treachery. Their breezy morning is abruptly shattered by a call from their mother, Susan, informing them that Manny has gotten sick and they are coming home right away. With their parents heading back, the brothers scramble to tidy up, ushering out any lingering partygoers before crucially switching Rodrick's bedroom door for the bathroom door, which sported the phrase, "Rodrick Rules." Unfortunately, their plan is thwarted when Frank discovers that the door fails to lock properly.
After this whirlwind episode, Greg seeks payback from Rodrick for assisting in the cleanup. Rodrick, in turn, shares his coveted "Rodrick Rules," an effortless guide to getting things done while doing minimal work. As Greg's impatience mounts, Rodrick introduces him to drumming, an activity that ultimately leads Greg to join forces with a fledgling band called Löded Diper, featuring an unexpected member: a man in his thirties.
At the same time, Greg agrees to help Rowley with a magic act for an upcoming talent show, skeptical of its potential success. Meanwhile, Frank, ever the watchful father, grows suspicious that the boys are hiding something, while Susan delights in their newfound camaraderie. When Frank questions Rodrick about the mysterious door, Greg concocts a plausible excuse about slamming it shut too hard, causing the malfunction. As their parents prepare for another escape—this time leaving the boys in Grandpa's care at the nearby nursing home—Rodrick exhibits particular enthusiasm about the situation.
During a chaotic moment at the nursing home, Rodrick distributes Mom Bucks, leading Greg to experience a series of misfortunes. When a game results in his pants getting wet, he rushes to change, accidentally entering the women's restroom and facing allegations of being a peeping tom. A frantic chase ensues through the seniors’ facility, culminating in Greg barely evading capture and returning to safety. Later, Grandpa offers insightful observations on family dynamics, praising the bond between Greg and Rodrick—a quality Frank seems to lack.
The following day at school, Rowley reminds Greg about his urgent life science project deadline, prompting him to seek the help of none other than Rodrick. Although Rodrick agrees, he does so in exchange for Mom Bucks, leaving Greg bewildered when the "help" manifests as a poorly executed project on plants sneezing—a far cry from the impressive outcome he had anticipated.
Angry at this betrayal, Greg confronts Rodrick to demand restitution in Mom Bucks, only to inadvertently run into Susan, revealing their blackmail scenario. Both boys end up grounded, with Greg still expected to join Rowley in the talent show. As a retaliatory move, Rodrick threatens to spill Greg's embarrassing secrets from his diary, including the restroom incident.
In an unexpected twist, Rowley accidentally sends incriminating photos, leading to wild rumors about Greg's supposed exceptional bingo skills and daring escape. Despite his newfound fame, Greg feels despondent about being forced to perform in the talent show beside Rowley.
Just as he's about to take the stage, Löded Diper approaches Greg with an enticing proposition: they need a new drummer, as their current fill-in, Larry, has a passion for magic that conflicts with drumming. Faced with the dilemma of seizing the spotlight or sticking with Rowley, Greg navigates his complex web of sibling relationships and high school social dynamics.
Battling his stage fright, Greg feels the pressure culminate in Rodrick's biting comments, prompting him to give up drumming. However, when he notices Rodrick leaving the show with a downcast face, Greg feels the urge to confront him, sharing his true motivations: a deep-seated desire for Rodrick's approval and fear of their bond weakening over time. Rodrick reassures him of his care and commitment to their friendship. With a newfound understanding, Greg reinstates Rodrick as the drummer—despite him being grounded—before returning to Löded Diper. While Frank and Susan extend Greg's grounding, Grandpa takes a moment to recognize Frank's efforts in raising two well-meaning boys, and Susan enthusiastically busts a move during the band's performance. In a surprising twist, Rowley’s magic show earns top honors, and Löded Diper's music gains popularity thanks to Susan’s vibrant spirit. Despite their differences, the sibling bond between Greg and Rodrick deepens, illustrating that even amid chaos, their brotherhood can overcome any obstacle.
