Jimmy Livingston, played by Jake Gyllenhaal, was born with a severe immunodeficiency, which confines him to a sterile dome in his bedroom. This unusual lifestyle earns him the nickname "Bubble Boy" amongst his neighbors. Raised by a devoutly right-wing Christian mother, he is limited to the pages of Highlights magazine and Land of the Lost for entertainment. However, everything changes when a new girl named Chloe moves in next door, sparking a deep connection despite his mother's reservations.
When Chloe announces her impending marriage to her boyfriend Mark in three days, Jimmy is crushed. They're left on sour terms after their heartfelt conversation, but everything shifts when he opens a gift she left for him—a homemade snow globe inscribed with "I Love You." Understanding how much he cares for her, Jimmy constructs a mobile bubble suit and escapes, hoping to stop her wedding.
His journey begins with him unable to afford a bus ride to Niagara Falls, but he is soon picked up by an overly enthusiastic cult on a quest for enlightenment. However, when he accidentally insults them by labeling their group a "cult," they abandon him in the desert. Meanwhile, his mother has realized her son is missing and sets out with her husband to find him.
As he wanders, Jimmy encounters Slim, a biker with a flat tire. Offering his help, they develop a friendship. Elsewhere, the cult leader, Gil, proclaims their messiah to be "the round one," and they regret leaving Jimmy behind and decide to search for him. Jimmy and Slim's journey takes them to Las Vegas, where they hope to earn enough money to reach their destination. However, things take a turn when Slim gets swept up in the Vegas lifestyle, prompting Jimmy to venture out alone.
In Vegas, Slim confronts the cult when they cross paths, but his bike is destroyed in the commotion. Enraged, Slim gathers a band of bikers to exact revenge. Meanwhile, while riding a scooter won in Vegas, Jimmy is spotted by his parents but veers off, ultimately boarding a train with circus freaks who are captivated by his uniqueness.
During his adventures, Jimmy finds himself in various predicaments, including a misunderstanding that leads the townspeople to evacuate a restaurant, unintentionally igniting a fire and resulting in a quarantine. He is rescued by Pushpop, the local Ice Cream & Curry truck driver, who promises to take him to Niagara Falls. However, due to circumstances, Pushpop cannot continue, and Jimmy sets out on foot, eventually connecting with Pappy, a cab driver, who agrees to drive him to his destination for $500.
To earn the money, Jimmy participates in a mud wrestling competition but encounters the cult once more. In a chaotic twist, the circus freaks come to his aid, disguising themselves to rescue him from the cult's plans of "liberation." With a mixed bag of allies—bikers, freaks, and the cult—an epic showdown unfolds.
On the final leg of his adventure, Pappy, who has become unresponsive during the drive to New York, forces Jimmy to leap out of the taxi before it ultimately crashes. Heartbroken, Jimmy tries to reach Chloe, but her fiancé Mark dishearteningly convinces him that she does not truly love him. In despair, he prepares to join Dr. Phreak and the circus when his parents catch wind of his location and rush to bring him home.
As Jimmy makes his daring escape, he finds himself airborne thanks to Pappy's brother, Pippy, who swoops in to help him reach Niagara Falls. Although he falls out into the tumultuous waters, he manages to resurface just in time to interrupt the wedding ceremony. In a bold move, he sheds his bubble suit and kisses Chloe, only to collapse, leading everyone to believe he has died. But his mother reveals the truth: Jimmy had developed an immune system at the age of four, a detail she had kept hidden to shield him from the harsh realities of the world.
With newfound love and understanding, Jimmy reconciles with his mother and resumes his embrace of Chloe. Their union culminates in a beautiful wedding, celebrating with an eclectic group of newfound friends and family. In a fitting conclusion, Jimmy's mother—revealed to be a former lover of Slim, now known as Wildfire—rides off with him, while Pushpop updates the cult’s beliefs, and Pappy and Pippy reconcile as they whisk Jimmy and Chloe off on their honeymoon.
