Chloe, a diamond-clad ultra-pampered Beverly Hills Chihuahua finds herself being "puppy-sit" by the niece, Rachel, of her owner when she leaves for Europe for one of her fashion shows. Rachel is enjoying her aunt's wealthy home but can't resist a weekend trip to Mexico with her friends. With Chloe in tote, Rachel's partying quickly disgusts Chloe and she decides she will go home herself. Chloe quickly gets lost in Mexico and thrown into a dog-fighting ring where she meets Delgado, an ex police K9 who is there and finds himself between his old enemy Diablo, the drug-lord's dog who ruined his career, and Chloe. After saving her and himself, Delgado agrees to help her get home and they begin their journey across Mexico for Beverly Hills. Meanwhile, Rachel has enlisted the help of her Aunt's gardener and Papi, the gardener's Chihuahua who's crazy about Chloe, to help find and save her. At the same time Diablo's master has learned of Chloe's identity and plans on dog-napping her for a big ransom. Along the way Chloe learns of her ancestry, her own strengths, and also finds a little love.