The Brody family's pet
Bloodhound Buddy chases a cat and is captured by other cats in an ambush. Cats and dogs are revealed to be highly intelligent and tech-savvy enemies capable of speech, waging war with covert operatives while concealing their true colors from humankind. After an
Anatolian Shepherd dog named Butch reports Buddy's capture to his superiors, the best canine agents are dispatched to complete Buddy's mission: to prevent the cats from making all humans allergic to dogs. At a local barn one month later, a litter of
Beagle puppies mocks their youngest brother for trying to escape captivity. A
Doberman Pinscher agent replaces the litter with a pack of
Miniature Pinscher agents, failing to notice the youngest Beagle. Carolyn, the Brodys’ matriarch, arrives to adopt a new dog and selects the Beagle, naming him Lou after her son Scotty sarcastically suggests the name "Loser", as Scotty is not ready for a new dog because he still misses Buddy and believes he might still come back. After detonating an explosive trap laid by cats for Lou, Butch – mistaking him for a trained operative – brings him to the dogs' underground network, and introduces agents Peek, a
Chinese Crested Dog, and Sam, an
Old English Sheepdog. Butch quickly realizes Lou is not the agent he was expecting, but his superiors order him to train Lou himself due to lack of time to find a replacement. Lou is briefed on the origins of the conflict between cats and dogs, dating back to
Ancient Egypt when cats ruled the world. Butch reveals that Buddy has escaped the cats and the spy trade, retiring to a
condo in
Boca Raton. Meanwhile, Mr. Tinkles, a white
Persian cat, plans to exploit the Brodys' patriarch Charles' research on dog allergies to conquer the world. His scheming is interrupted by Sophie, his comatose owner's maid, who enjoys dressing Tinkles in embarrassing costumes. Tinkles orders his sidekick Calico, an
Exotic Shorthair, to send
Devon Rex ninjas to steal the research. Lou foils the theft and meets a former agent and Butch's ex-girlfriend Ivy, a
Saluki who encourages him to bond with Scotty. Mr. Tinkles contracts a
Russian Blue mercenary named Dimitri Kennelkoff, who tricks Lou and places a bomb on Brody's lab door. Kennelkoff battles Lou and Butch, damaging the Brodys' house until Butch disables the bomb and captures Kennelkoff. During the interrogation, the dogs recover a note by Mr. Tinkles from Kennelkoff's stomach. After a breakthrough involving Lou playing with Scotty, Charles' machine finally finds the formula to a cure for human allergies to dogs. Having bugged the house, Mr. Tinkles and Calico spring a trap for the Brodys. First, Mr. Tinkles travels to a
Christmas tree flocking plant under the guise of the plant's comatose owner, Mr. Mason, and sends the employees home, then lures the Brodys with fake tickets to a soccer exhibition game, capturing the family. The dogs receive a video from Mr. Tinkles demanding Charles' research as a ransom for the Brodys, and dogs around the world assemble at a meeting, led by a
Mastiff. When the assembly decides not to surrender the formula, Lou confronts Butch. Revealing that he was abandoned by his owner, the unsympathetic Butch leaves Lou behind. Desperate, Lou brings Mr. Tinkles the research and is double-crossed. Butch, realizing what has happened, stages a raid of Mr. Tinkles' factory where
mice are being prepared to spread the mass-produced allergy. While Butch, Ivy, Peek, and Sam fight Tinkles' cat forces, Lou frees the Brodys and Calico, who was betrayed by Tinkles, revealing to the family that he can speak. Lou defeats Tinkles but is struck by an excavator as an explosion destroys the whole factory. Butch rescues the seemingly dead Lou, tearfully admitting that Lou was right to love his adoptive family, and Lou awakens. He decides to return to a normal pet's life with the Brodys until he can serve as a full-grown agent. Meanwhile, Tinkles is sent to live with Sophie and her three sisters, where he is dressed in even more humiliating outfits as punishment for his actions against the dogs. == Cast ==