Vivian Ashe (Jamie Lee Curtis) leaves her pet chihuahua Chloe, (Drew Barrymore) with her irresponsible niece Rachel (Piper Perabo).

Meanwhile, Rachel is searching for Chloe with Sam (Manolo Cardona) and Papi (George Lopez), landscaper and dog before Aunt Viv gets home.

When Delgado was talking to his friend from when he was in the Mexican Police, Chloe encounters a pack rat named Manuel (Cheech Marin) trying to steal her diamond collar.

El Diablo (Edward James Olmos), a fierce Doberman Pinscher, is sent by the dog fight ringleader to capture Chloe for the reward.

Papi mentions that there might be a few miniature baby Chihuahuas in their futures, the two stray dogs that Sam and Rachel adopt on the trail of Chloe go to good homes too, El Diablo is adopted by a lady who has a passion for fashion, and Sam and Rachel start dating.

However, Papi shows a soft side for the pups and occasionally tells them of their ancient ancestors, the Chihuahua Warriors.

Aunt Viv (Susan Blakely), Chloe's owner, is in the rain forest for the next 6 months with her niece, Rachel (Erin Cahill) searching for plants for medical research.

During this time Sam (Marcus Coloma), Papi's owner and Rachel's boyfriend, is caring for the whole chihuahua family.

Sam takes Chloe, Papi and the puppies back home to meet his parents, Mr. and Mrs. Cortez (Castulo Guerra and Lupe Ontiveros).

Sam finds out that his parents are struggling to pay the mortgage on their house and the bank plans to take their home and sell it.

Later, Papi initially wins the dog show, but is later disqualified due to lack of breed papers, losing to an arrogant and vain French poodle named Appoline (Bridgit Mendler).

Papi comforts her, telling her about how he was a chamberlain at a friend's Quinceanera when Pedro finds a picture in a box marked "DO NOT OPEN".

Back at home, Rosa fakes being sick to avoid going to school but when Papi says she will have to go to the vet, she claims she is feeling better.

But in the midst of the party planning, Papi continues to be his paranoid self and was pressured due to the lot of errands he has been working on.

Papi tells Pedro to open the gate, and Delgado appears with the rival hotel manager, Montague, hung upside down.

An animated short titled Legend of the Chihuahua (2009) was released as a bonus feature with the first film on DVD.

The series was developed by Tad Stones and Bento Box Entertainment and would have aired on Disney Junior.