Chance, narrated by Michael J. Fox, is an immature American Bulldog who treats his human family with a casual shrug, showing little interest in his owner Jamie Seaver Kevin Chevalia or the idea of belonging to a family. He shares the house with Shadow Don Ameche, a wise old Golden Retriever owned by Jamie's brother Peter Burnford Benj Thall, and Sassy Sally Field, a pampered Himalayan cat owned by Peter and Jamie's sister Hope. That morning, their mother Laura Burnford-Seaver Kim Greist marries Bob Seaver Robert Hays. The wedding cake is devoured by Chance in front of all the guests, a mischievous act that foreshadows the chaos—and loyalty—that will follow.
Shortly after the wedding, the family must relocate to San Francisco for Bob's job, leaving the pets at a ranch belonging to Kate Jean Smart. Shadow and Sassy miss their owners immediately, but Chance sees it as a chance to relax and go it on his own. Later, Kate heads off on a cattle drive, leaving Frank Gary Taylor in charge. A miscommunication leaves him believing the animals have been taken along, so the trio feels abandoned and vulnerable. Shadow, refusing to think his boy would abandon him, decides to make his way home, and Chance and Sassy decide to accompany him on this trek.
They plunge into the rugged Sierra Nevada, with Shadow taking the lead. After a tense night amid unknown woodland sounds, the group stops for breakfast by a river and is interrupted by two black bear cubs, followed by a large brown bear that forces them to retreat. At another river, Sassy hesitates to swim across and instead tries to cross a wooden path downstream; the makeshift bridge breaks, and she plunges into the water. Shadow lunges to save her, but she disappears over a waterfall, presumed dead by the others. Crushed by guilt, Shadow and Chance press on without her, unaware that Sassy has survived and is found by an old man named Quentin William Phipps, who nurses her back to health.
Over the next two days, Shadow and Chance struggle to find food and narrowly escape a mountain lion that chases them to a cliff's edge. Shadow devises a clever trap, using rocks to create a seesaw that lures the cougar away; while Shadow acts as bait, Chance hits the end of the rock and sends the mountain lion into the river. The celebratory barking from the dogs reaches Sassy, and she reunites with her companions.
Meanwhile, back home, Kate returns to her farm; Frank confronts her about the missing note, and she insists she did not bring the animals. She contacts a forest ranger and informs Bob that the animals are lost in the woods. The family grieves, and Peter argues with his stepfather over whether they should search for the pets, while Bob sends out flyers to park rangers in hopes of locating them.
On their journey, the animals stumble upon a missing little girl, Molly [Mariah Milner], and they loyally stand guard over her through the night. In the morning, Shadow finds a rescue party and leads them back to Molly. Two forest rangers recognize the trio from the flyers and escort them to an animal shelter, where staff remove Chance’s quills after the porcupine incident. Believing they’re in an animal pound, the trio panic; Sassy escapes and later returns to free Shadow, and together they reclaim Chance. Unbeknownst to the animals, their owners are already on the way to reclaim them.
After finally reaching their hometown, the animals cross a train yard, where Shadow injures his leg by falling into a muddy pit. He tells the others to go on, but Chance refuses to abandon the elder dog. As dusk settles, Chance and Sassy make it home and are joyfully reunited with their family. Shadow limps into view shortly after, rejuvenated by the reunion with Peter. The film closes with Chance reflecting on the lessons he has learned and his renewed appreciation for his family, before he bolts into the house at the scent of food.
