Chloe's owner, Aunt Viv, leaves her Chihuahua with her irresponsible niece, Rachel, to dog-sit. Sam the landscaper's male Chihuahua, Papi, notices Chloe and immediately develops a crush on her, though she initially rejects him.
Rachel later decides to take Chloe to Mexico and leaves the pooch, who sneaks out and gets stolen. Chloe ends up getting tossed into a dog-fighting ring owned by Vasquez, left to defend herself from a Doberman Pinscher named El Diablo. Fortunately, she is rescued from the dogfight by a German Shepherd named Delgado.
Chloe thanks Delgado for saving her and asks him if he could help her find her way back to Beverly Hills. Delgado refuses at first, but after Chloe insists that she was dognapped and being pursued by Diablo, the police dog reluctantly helps her. Along the way, Chloe constantly pesters Delgado by asking him agitating questions. Later, Chloe gets tricked by a rat named Manuel and an iguana named Chico, who talk her into giving them her diamond collar. When Delgado finds out, he quickly becomes furious with her because that collar was evidence to where she lived.
On their journey to Beverly Hills, Chloe and Delgado become stranded in a desert after jumping off a train they stowed away on earlier. They eventually encounter a large group of stray Chihuahuas led by Montezuma, who save them from three vicious mountain lions. Chloe and Delgado then stay for a short time at the Chihuahua pack's birthplace.
Later, Chloe and Delgado arrive at a national park in Mexico, where Chloe is recognized by an employee. Unfortunately, Chloe is found and taken away by El Diablo to Vasquez and his henchman, Rafferty. Rachel and the landscaper go to get Chloe and Papi (who set out earlier to find his "Mi Corazon"), but Delgado beats them to her. They end up in an old ruin where Chloe almost gets locked in a cage. Fortunately, Papi arrives and helps Chloe escape, although he gets captured as well. When Chloe frees him, she finds her inner bark and scares Vasquez away, and with the help of Papi and Delgado, they mange to defeat Diablo. Rachel and Sam find Chloe and Papi and take them both home.
Back in Beverly Hills, Chloe and Papi relax on the patio. Chloe thanks Papi for his help and tells him that she loves him in Spanish, and she licks him down to the ground as her way of showing her love. Before the end credits, Papi explains what happens to the dogs (Chloe's friends that she met in Mexico) and Chloe's Beverly Hills friends, and he and Chloe have five puppies.
Chloe reappears in the second film with her husband, Papi. They have five puppies named Papi Jr., Lala, Rosa, Ali, and Pep, which they try to keep up with. Chloe believes that Papi is too easygoing and suggests he starts showing their kids a little discipline. Papi is reluctant to do so at first, but he eventually comes around in the end. Later, Chloe and Papi, along with Delgado and Pedro (Papi's adoptive brother), participate in a dog fashion show to win a large cash prize that would save Sam and Rachel's family house. Chole becomes disqualified after she plays a clinker on the piano. Though Papi had initially won, because of the lack of breed papers, he is disqualified as well. Due to these actions, the dogs lose to an arrogant French poodle named Appoline, much to their chagrin.
Eager to help out with Delgado's deep situation concerning his sons: Alberto and Antonio (whom he had abandoned as puppies at a police station for protection), Papi and Chloe's kids venture out and eventually find some bank robbers who had stolen a large sum of money. The puppies stow away in one of the bags, but are later found out by the robbers. Papi and Chloe soon discover their kids missing, and they, along with Pedro and Delgado, set out to look for them. The dogs eventually locate the puppies and defeat the bank robbers. Papi scolds the kids for running off, but Chloe tells Papi that they did manage to capture the robbers and were trying to save their family home, so Papi lets the kids off lightly. The dogs return home to find that they have been awarded more than enough money to save Sam's family house. Chloe and the dogs, along with their human owners, celebrate their victory and Sam and Rachel's engagement and live happily ever after.
She appears in the third film with Papi and the puppies. Her role is not as large in this film. When everyone moves into a luxury hotel, Chloe tells Papi that even though he's a great teacher, she felt like they needed a real dog school to go to. She was also worried that Rosa felt like she was the "runt of the litter." At the hotel, Chloe is seen posing for photos and playing the piano. She and Oscar are talking as they approach the mudbath, only to find Papi spying on them. She then walks away from him without saying anything.
Later, after finding out that Rosa saved Charlotte from drowning in the big pool, Chloe decides that Rosa should still have her fiesta for her sweet 15. When hearing that Sam and Rachel lost their jobs at the hotel, she, Papi, Pedro, and Charlotte decide to make things right and repair the garden. At the party, after Jenny and Oscar got arrested, Chloe decides to make Papi a real teacher again and is then seen celebrating with everyone else.