In the opening scene, we are introduced to Rusty Griswold (Ed Helms), a dedicated pilot for Econoair, a regional airline. He embarks on an 18-minute flight from South Bend, Indiana to Chicago. Upon landing, while waiting for the Crew Shuttle, he experiences an unpleasant encounter with a rival pilot (Ron Livingston), who bullies him out of line.
Back at home, Rusty's family dynamic is anything but smooth. He is married to Debbie (Christina Applegate), and their home life includes two sons; the older, awkward James (Skyler Gisondo), who is being bullied by his younger brother Kevin (Steele Stebbins), who goes as far as writing "I have a vagina" on James's beloved acoustic guitar. Trying to help, Rusty scribbles over the offending word, replacing "vagina" with "penis."
That evening, the Griswolds share dinner with their neighbors, the Petersons (Keegan-Michael Key and Regina Hall). Jack Peterson seems to have a great rapport with his son, having built a go-kart together and engaging in playful banter. While Rusty tries to showcase his own father-son relationship with James and Kevin, it becomes clear that Kevin would rather not partake in such theatrics, and James struggles with his attempts at bonding. During the meal, Nancy Peterson covertly throws shade at Debbie for not liking her Instagram posts from a recent family trip to Paris and mentions that Debbie’s weight loss has made her wedding ring uncomfortably loose. Rusty steps out for a moment but returns just in time to overhear Debbie confess her disappointment about how the family exclusively vacations at their cabin in Cheboygan, Michigan every year. She longs for a change.
Determined to create a memorable family trip, Rusty rents a car, ultimately settling on a bizarrely designed vehicle named a Prancer, which hails from Ukraine. This peculiar car features two gas tanks, a hybrid system, an array of outrageous buttons—among which are a swastika and a muffin—and an even crazier outlet system equipped with corkscrew plugs. It becomes Rusty’s mission to recreate his cherished childhood vacation to Walley World in Los Angeles, a place that holds a special significance for him.
During their first day on the road, Rusty attempts to bring the family together through music, leading a sing-along of the song Kiss From a Rose by Seal, to muted reactions from his family. He proudly reveals the car's standard CB radio, inviting connection with truckers. He engages a truck behind them, complete with a teddy bear mounted on the grill, in a light-hearted exchange about the highway’s safety. In a rather embarrassing moment, Kevin humorously questions whether it's true that all truckers are rapists, leading to an awkward apology from Rusty.
After stopping for lunch at a diner in Missouri, the family crosses paths with the Teddy Bear Truck once again in the parking lot. The story takes an interesting turn as James spots a cute girl in a nearby Jeep, and for a fleeting moment, they share a wordless flirtation—interrupted by Kevin’s childish antics as he throws a plastic bag over James's head.
When they arrive in Tennessee, Rusty decides to divert their course to introduce the boys to their mother’s old college sorority house. To Rusty’s surprise, he uncovers a “chug run,” an outrageous obstacle race for college students fueled by beer, organized to raise funds for a misnamed cause labeled Ass Burgers instead of Aspergers. Embarrassingly, Debbie divulges to Rusty her past—as the inventor of the chug run herself. To prove she's still spirited, she daringly enters the competition, only to erupt in uncontrolled projectile vomiting shortly after she guzzles her beer.
The family's road trip continues with a relentless pursuit from the Teddy Bear Truck, which tailgates them aggressively, leading Rusty to resort to a quick getaway maneuver inspired by Fast and the Furious. In a misguided attempt, he pulls the emergency brake while turning, resulting in the Prancer rolling over before miraculously landing on its wheels.
As they check into a motel, Rusty feels a sense of inadequacy while Debbie reminisces over her experiences with numerous past relationships compared to his relatively few conquests. He tries to spice things up by suggesting a romantic shower, but their dirty living environment proves too off-putting for such plans to materialize. Meanwhile, James finds himself bonding with the girl from the Jeep, named Adena (Catherine Missal), but Rusty’s awkward attempts at parental involvement only scare her away.
Next on their journey is a visit to Rusty's older sister Audrey (Leslie Mann) and her ridiculously attractive husband, Stone Crandall (Chris Hemsworth). While it appears that Debbie is somewhat smitten by Stone’s charms, Rusty decides to make another diversion first.
They stop to explore a hot spring, but the long wait causes Rusty to seek out a shortcut. After receiving dubious directions from a local accompanied by a pet rat, the Griswolds unwittingly find themselves at a septic dump instead of a hot spring. To their dismay, they discover not only the unsightly conditions but that their belongings have been stolen upon returning to the Prancer, which now sports a crude drawing of a penis painted on its side.
Upon reaching Audrey and Stone's luxurious home, the family struggles to justify their appearance, but, much to Rusty’s chagrin, Kevin spills the beans about the devilish excursion they’ve had. Stone’s charm is palpable, and it’s evident that Rusty feels overshadowed. Later on, Debbie admits her frustrations about her lost wedding ring, which she confesses has been loose for some time. In a more intimate moment shared between Rusty and Debbie, Rusty ironically awakens to help Stone fetch cattle; instead of riding horses, they’re on 4-wheeler quads, leading to an unfortunate encounter with a steer that meets a messy end.
Their travels continue as they stop at a reservation near the Four Corners Monument. Rusty, desperate for a thrill, proposes a romantic escapade outside that will cover all four states simultaneously together with Debbie. However, they find themselves caught in the act when a group of naked couples sharing the same idea is interrupted by police from four different states. In the chaos, they manage to evade arrest and flee.
Meanwhile, James encounters Adena once more, and through a heart-to-heart, he addresses his challenges with his brother Kevin, ultimately deciding to stand up for himself. Their jaunt takes them to the Grand Canyon, where danger ensues during an exhilarating but reckless rafting experience guided by a recently heartbroken man. Finally reaching their breaking point, Rusty confronts the reality that his vacation dream might be slipping away; the family runs out of gas, leading Rusty to abandon their hopes of making it to Walley World.
Feeling despondent, Rusty distances himself from the family that he yearns to connect with. Just when things seem hopeless, the Teddy Bear Truck reappears, and its driver, Norman Reedus, brings Debbie's lost ring back, providing not only a resolution but ultimately a ride towards San Francisco. Rusty and the family reconnect and make a promise to keep their passion for adventure alive. The vacation wraps up with a heartwarming visit to their parents—Clark and Ellen Griswold (Chevy Chase and Beverly D'Angelo), and after a somewhat comical series of events unfolds, Rusty resolves to finish what he started and reclaim their trip to Walley World.
They eventually arrive at the park, only to find themselves stuck in an exasperating five-hour line for a roller coaster ride. Just as they reach the front, the rival pilot from earlier sneaks in with his family, using their Fast Passes, creating an intense showdown between the Griswolds and this encroaching family, culminating in a wild and desperate act that allows them to secure their place on the coaster as the park is about to close.
As the ride begins and climbs the first hill, the Griswolds join in harmony, singing Kiss From a Rose at last. Yet, misfortune strikes, and the roller coaster halts mid-ride. The following evening, Rusty is left to fly the boys back home, while he and Debbie prepare for their romantic trip to Paris, utilizing his airline connections for seating—a scheme that, while not quite ideal, leads them to their own unique adventure in life and love.
