Jimmy Livingston is a boy born without an immune system. Because of this, he is forced to live in a bubble dome in his bedroom in Palmdale, California (Bubble Boy was filmed mostly in Palmdale, California.) For this reason, his neighbors nickname him Bubble Boy. Jimmy's mother, a devout right-wing Christian and antisocial, only exposes him to Highlights magazine and the Land of the Lost television show for entertainment. When he is a teenager, a girl named Chloe moves in next door. Jimmy is immediately taken with her, even though his mother warns him that Chloe does not seem like the kind of girl Jesus would befriend. Despite his mother's warning, Jimmy and Chloe become good friends. They develop a close relationship. At one point, Chloe tries to come into his bubble, but Jimmy is afraid of contamination and does not let her in.

One day, Chloe visits Jimmy and tells him that she is leaving for Niagara Falls to marry her long-time boyfriend, Mark. She announces that the wedding will take place in three days. She then asks Jimmy if he thinks that Mark is "the one," but Jimmy refuses to answer her. When Chloe tries to give him a gift, Jimmy refuses to accept it. Chloe is upset and decides to exit, leaving the present with Jimmy. Later, Jimmy opens the present, a homemade snow globe that contains miniature models of Jimmy and Chloe sitting on the phrase I Love You. Jimmy realizes that Chloe cares for him deeply. Overcome with guilt for having driven Chloe away, Jimmy builds a mobile bubble suit and sneaks off into the night, determined to stop the wedding. Throughout his journey to Niagara Falls, Jimmy runs into a wide variety of people:

One his first day out, after being rejected for a bus ride to Niagara Falls for not having enough money, by a very low-pan Bus Stop man, Jimmy is picked up by a group of people known as the Bright and Shiny Society, a cult who are embarking towards enlightenment by the way of the "clubda," and give Jimmy the nickname of "Todd." But after Jimmy unintentionally offends the cult, he is thrown out of the bus and marooned in the middle of the desert. Shortly after, Jimmy's mother discovers her son has gone missing and so she and her husband set off to find Jimmy themselves. Jimmy, after being chased by a hungry vulture then meets Slim, a hispanic Biker. Jimmy offers to fix his bike which has broken down and the two become from friends, Slim tells Jimmy about someone he loved named "Wildfire" just like Jimmy did with Chloe, but never expressed his feelings. Elsewhere, the Bright and Shiny Society has proclaimed that "the round one" is their identified chosen one and that whoever objects will be mutated. the group whom abandoned Jimmy now regret their mistake and set off to find him once again.

Later that night after Jimmy fixes his bike, Slim takes Jimmy to Las Vegas in hopes of scoring some money to get to Niagara Falls. However Slim gets caught up into gambling and Jimmy has no other choice but to continue going on his own. The Bright and Shiny Society confront Slim looking for Jimmy, but Slim defends his friendship with Jimmy and prepares to attack them only to have his bike destroyed by the cult. Enraged, Slim rallies a gang of motorcyclists to get even with the Bright and Shiny Society. Jimmy while traveling on a bicycle gets a close call with his parents who are looking for him, but gets separated and bounces into a train carrying a group of circus freaks that belong to Dr. Phreak's traveling sideshow circus. The next morning, Dr. Phreak finds Jimmy and abuses him, demanding that he's keeping him in his circus seeing as he's trapped in a bubble. Jimmy refuses, knocking him unconscious and freeing the other circus freaks from his abusive ways.

Jimmy then wanders into a restaurant where an Indian man is being abused by the town's people, the people suddenly try to provoke him, but when Jimmy explains that he doesn't have an immune system, the people panic believing that a "munity" is a virus and proceed to lock him in the restaurant and quarentine it. Suddenly, an oil lamp is dropped and the restaurant goes up in flames. Luckily, Jimmy is saved by the Indian man, who introduces himself as Pushpop, an Ice Cream & Curry Man. After escaping from the town as it burns with the restaurant, Pushpop proclaims that he's greatfull to Jimmy for protecting him back at the restaurant and agrees to take him to Niagara Falls. Meanwhile, the Freaks whom Jimmy saved are having trouble deciding where to go, Jimmy's parents run into Dr. Phreak, whom Jimmy's mother mistakes for a child and bring along with them. Elsewhere in Niagara Falls, Chloe is regretful for having to marry Mark as she is still attached to Jimmy. On the journey, Pushpop accidentally runs over a cow and feels too guilty to continue the journey, but gives Jimmy a frozen ice cream bar as a "thank you" from earlier before.

Jimmy's journey has now taken him to Illinois where he needs $500 dollars in order to get to Niagara Falls by Taxi. Jimmy takes a challenge to win the $500 dollars by Mud Wrestling with two women in a Japanese casino. Jimmy eventually wins, but just as he is about to leave he is picked up again by the Bright and Shiny Society. Still proclaiming his as their chosen one, they plan on "releasing" Jimmy from his bubble, which could kill Jimmy due to him lacking an immune system. Luckily, the freaks have followed Jimmy and realizing he's in danger, disguise themselves as members of the cult. Tricking the cult into believing they're mutated, Jimmy and the Freaks escape during the commotion only to run into Slim and his bikers, (as well as Pushpop who offered them Ice Cream & Curry.) The Bikers, the Freaks, and the Cult all get into an all-out brawl with Jimmy finding the Taxi and escaping during the madness. The Taxi Man, known simply as "Pappy" explains that he too was in love with a woman until his Brother, "Pippy" stole her from him and has also lived in regret for his lost.

On the last day in his journey, Pappy and Jimmy have now arrived in New York and Jimmy tries to call Chloe to tell him of his success, only to reach her fiancée Mark, who rudely convinces him to give up due to him being trapped in his bubble and that Chloe doesn't really love him. Jimmy becomes depressed at this assumed rejection and is discovered by his Parents who prepare to take him home. However, Jimmy's Father (whom is more level-headed than his wife) feels sorry for Jimmy that he is being forced to give up when he is so close and after being put through so much already. Jimmy's Father then releases Jimmy to continue his journey now with everyone in pursuit: (Jimmy's Parents, The Bright and Shinies, Silm and his Bikers, The Freaks, and Pushpop.) Suddenly, A biplane swoops down and picks up Jimmy, it's Pappy's Brother Pippy! He reveals that he met and married a different woman that Pappy had in mind named "Poonany." Finally, Jimmy reaches Niagara Falls but is suddenly dumped out of the plane and into the falls itself! Jimmy risks drowning but remembering Slim's words of advice, survives the Falls.

Jimmy stops the wedding at the last moment and takes off his bubble suit, allowing him to touch the girl he loves one last time. He then collapses and presumably dies in front of everyone in the church, as well as all the people who came with his on his journey. Jimmy's father then forces Jimmy's mother to confess the truth: Jimmy had developed a fully functional immune system when he was four years old, and Jimmy realizes that he is not dead at all. It is revealed that Mrs. Livingston had hidden this fact from Jimmy to protect him from the world. Jimmy forgives her and leaves the church with Chloe. Later, Jimmy and Chloe are married with all of their new friends in attendance. Jimmy's Mom (who is revealed to be Slim's "Wildfire") joins up with Slim. Pushpop becomes the new leader of the Bright and Shiny Society and converts it into a more decent religion. Even Dr. Phreak becomes more friendlier to his band of freaks (Thanks in part to Jimmy's motherly care.) Then, Pippy, Pappy (who've reconciled their past relationship) and Poonany drive Jimmy and Chloe to their honeymoon (with the Vulture that chased Jimmy earlier in pursuit.)

The film opened at #13 at the U.S. Box office raking in $2,038,349 USD in its first opening weekend.

The Walt Disney Company, Touchstone's parent, was criticized upon its release, partly because it makes light of a real-world condition, and partly because of the way religions are depicted.[citation needed]