Born without an immune system, Jimmy Livingston lives in a sterilized dome in his bedroom in his home in California, earning him the nickname "Bubble Boy" by his neighbors. His overbearing and devout Christian mother only exposes him to Highlights magazine and Land of the Lost for entertainment. When he is a teenager, Jimmy is immediately taken with Chloe, who moves in next door, and the two become friends despite his mother's discouragement. When Chloe leaves for Niagara Falls to marry her boyfriend Mark in three days' time, Jimmy realizes that Chloe cares for him and builds a mobile bubble suit, determined to stop the wedding.
Along the way, Jimmy is picked up by a cult called Bright and Shiny but is abandoned in the desert when he offends them. He finds a new ride with Slim, a biker who speaks fondly of his old flame "Wildfire" upon hearing Jimmy's story. The Livingstons pursue Jimmy, along with the cult members whose leader Gil believes "The Round One" to be the group's messiah. Jimmy leaves a distracted Slim behind in Las Vegas and continues on using a scooter he wins at a casino. Encountering his parents on the road, Jimmy is struck by their vehicle and bounced aboard a train belonging to Dr. Phreak, who shows "freaks" to the public for money. When Phreak tries to recruit Jimmy, Jimmy knocks him unconscious, which allows the freaks to go their own way. They choose to trail Jimmy along with the other parties in pursuit.
Jimmy is picked up by Pushpop, an Indian ice cream truck driver, but has to continue on foot when they hit a cow on the road. Winning $500 in a mud wrestling competition, Jimmy pays taxi driver Pappy for a ride but is cornered by the cult members. He slips away during the group's skirmish with the freaks and Slim's gang. After Pappy appears to have died at the wheel, Jimmy tries to call Chloe from a gas station in New York only to reach her fiancé Mark, who rudely convinces him that Chloe doesn't love him. Discouraged, Jimmy intends to return home with his parents, but encouragement and an opening provided by his father Morton allows him to escape on a plane piloted by Pappy's twin brother Pippy.
When Pippy becomes lifeless over Niagara Falls, Jimmy survives the fall and arrives at the church in time to stop the wedding. Abandoning his bubble suit, he embraces and kisses Chloe before collapsing. At Morton's insistence, Mrs. Livingston confesses that he had already developed an immune system when he was four and has been perfectly fine all along. She had kept him isolated only due to her overprotective nature.
Jimmy and Chloe are married with all the people encountered during his adventure in attendance. Recognized as the former "Wildfire," Mrs. Livingston re-embraces her rebellious side and prepares to depart with Slim on his bike along with Morton. Jimmy and Chloe discover Pippy and Pappy – both of whom merely fell asleep instead of dying – as they ride off to begin their honeymoon.
