In the 1930s, shy eight-year-old Carl Fredricksen idolizes famous explorer Charles F. Muntz. When Muntz is accused of fabricating the skeleton of a giant exotic bird he says he discovered at Paradise Falls, he vows not to return until he captures one alive. One day, Carl befriends an extroverted girl named Ellie, also a Muntz fan. She shares her scrapbook with him and confides to Carl her desire to move her “clubhouse” — an abandoned house in the neighborhood — to a cliff overlooking Paradise Falls.
Carl and Ellie grow up, marry, and live in the restored “clubhouse”. After Ellie suffers a miscarriage and they are told they cannot have a child, the couple remembers their childhood dream of visiting Paradise Falls. They save for the trip, but repeatedly have to spend the money on more pressing day-to-day needs. They nonetheless live a happy life. After retiring from their jobs at the local zoo, Carl buys plane tickets to Paradise Falls, but Ellie suddenly falls ill and dies.
Years later in the present day, Carl still lives in the house by stubbornly holding out while the neighborhood around him is being replaced by skyscrapers. When he accidentally injures a construction worker, the court deems him a public menace and orders him to move to a retirement home. However, Carl resolves to keep his promise to Ellie by turning his house into a makeshift airship, using thousands of helium balloons saved from his old job as a balloon salesman. Russell, a young “Wilderness Explorer” who visits Carl so he can earn his final merit badge for “Assisting the Elderly”, becomes an accidental stowaway.
The flying house encounters a cumulonimbus storm and ends up high above South America. The house lands on a tepui opposite Paradise Falls. Carl and Russell harness themselves to the still-buoyant house and begin to walk it across the mesa, hoping to reach the falls before the balloons deflate. Russell encounters a tall colorful bird whom he names “Kevin”, who is trying to gather food for her chicks. They then meet a Golden Retriever named Dug, who wears a special collar that allows him to speak, and who vows to take the bird to his master. The next day, they encounter a pack of aggressive dogs led by Alpha, a Doberman Pinscher, and are taken to their master, who turns out to be an elderly Charles Muntz.
Muntz invites Carl and Russell aboard his dirigible, where he explains to them that he is still desperately searching for the giant bird he promised to bring back, which is revealed to be of Kevin’s species. Russell notes the bird’s similarity to Kevin and Muntz becomes hostile, thinking they are attempting to capture the bird for themselves—like many other visitors he implies to have killed. Realizing that Muntz has become insane, Carl and Russell flee with Kevin and Dug, but Muntz eventually captures Kevin and starts a fire beneath Carl’s house. Carl saves the house, allowing Muntz to leave with Kevin, and Russell becomes upset at Carl’s selfishness. The group finally arrive at Paradise Falls and park the house, where Carl sadly looks through Ellie’s childhood scrapbook, only to find that she has filled in the supposedly blank pages with photos of their happy marriage, along with a final note thanking Carl for their “adventure” and encouraging him to move on from her death.
Reinvigorated, Carl goes outside to see Russell sailing off with some balloons and a leaf blower to rescue Kevin. By throwing out his furniture and keepsakes, Carl lightens the house enough for him and Dug to follow. Russell is captured by Muntz, but Carl and Dug manage to board the dirigible, tether the house, and free Russell and Kevin. Dug saddles Alpha with the “cone of shame” and unexpectedly becomes the dogs’ new leader. Muntz furiously pursues them around the airship and further cripples the flying house, cornering Kevin, Dug, and Russell inside. When the three leap back onto the dirigible, Muntz leaps after them and inadvertently gets caught on some balloon lines, causing him to fall to his death. The house, having lost too many balloons to fly, descends out of sight through the clouds.
Carl and Russell reunite Kevin with her chicks and fly the dirigible back home. Russell receives his “Assisting the Elderly” badge, and Carl presents Russell with the “Ellie Badge” — a grape soda bottle cap that Ellie gave to Carl when they first met. Carl, Russell, and Dug later sit together, eating ice cream and counting approaching cars like Russell used to do with his dad. Unbeknownst to Carl, the house has landed on the cliff beside Paradise Falls exactly where Ellie had pictured it, fulfilling Carl’s promise. The end credits show snapshots of Carl, Russell, and Dug happily enjoying life together.