In Beverly Hills, California, wealthy heiress Vivian “Viv” Ashe leaves her richly pampered pet chihuahua, Chloe, with her irresponsible niece, Rachel, while she embarks on a business tripfor ten days.
Papi, the gardener Sam’s pet Chihuahua of Mexican descent, has an unrequited crush on Chloe, to which she is disgusted by. Rachel decides to go to Mexico with her friends and stay at a hotel by the beach.
When Rachel leaves Chloe alone in the hotel room to go dancing at a club, Chloe goes looking for her. Chloe gets dog-napped as she tries to find Rachel and is sent to the dog fights in Mexico City.
There, she meets a street-smart German Shepherd named Delgado. Rachel comes back to the hotel and is frantic when she finds Chloe missing.
Chloe is picked to fight in the pit against El Diablo, a fierce Argentinean-Bolivian Doberman Pinscher. Delgado helps her escape the dog fights, unleashing the other dogs from their cages and unlocking the ring to allow both Chloe and himself to flee.
After several arguments, he then decides to return her to Beverly Hills safely.
Meanwhile, Rachel and Sam go to the Mexican police and offer rewards in an effort to find Chloe. El Diablo is sent by the dog fight ringleader, Vasquez, to capture Chloe and obtain the reward from Rachel.
Delgado and Chloe arrive at Puerto Vallarta, where Chloe is caught by El Diablo but rescued.
She then waits for Delgado to find help but is tricked into handing over her diamond-studded necklace to con artists Chico, an iguana, and Manuel, a pack rat who claims to be from the Yucutan.
Chloe and Delgado sneak onto a train heading towards the border, but they are caught and are forced to jump out, eventually arriving in the barren deserts of Chihuahua, where Delgado explains that he was a former police dog; he was retired after he lost his sense of smell during a raid.
Rachel and Sam are in Puerto Vallarta and find that Chloe was spotted in the state of Chihuahua.
After tracking Chloe and Delgado from Mexico City, El Diablo arrives in Chihuahua and attempts to capture Chloe, but Papi saves her and ends getting captured in a cage inside an abandoned Aztec temple, but Delgado comes to rescue the two and is briefly defeated.
Chloe then rescues Papi, but Delgado discovers that El Diablo had vanished. Rachel finds Chloe, and Vasquez get arrested by the police.
Chloe returns safely to Beverly Hills without Vivian finding out what happened and accepts a romantic relationship with Papi, as well as Rachel with Sam.
The characters’ fates are later revealed: Delgado returns to being a police dog in Mexico. El Diablo is recaptured by Delgado and is adopted by a rich lady who “had a passion for fashion”.
Chico and Manuel move to Beverly Hills and become rich. Teenager Angus (Bradford) adopts a Yellow Labrador Retriever and names him Yellow.
Several days later, while traveling along the coast of British Columbia with Angus’s father, the boy and dog become stranded when turbulent waters capsize their boat.
Angus’s parents relentlessly badger rescue teams. Angus, schooled by his father in wilderness survival skills, and assisted by the intelligent Yellow Dog, tries to attract rescuers.
Starvation, freezing temperatures, violent rainstorms, and a pack of wolves test Angus’ and Yellow’s courage and abilities to survive as they journey through the Canadian wilderness. Angus is eventually rescued but has to leave Yellow behind. Angus is later shown at home sitting on his porch; he blows his dog whistle and Yellow comes running back home. He and his family all rejoice over the return of Yellow.