Plot
Unbeknownst to humans, cats and dogs are, in reality, highly intelligent and tech-savvy enemies waging war on each other with covert operations. The Brody family find their pet Bloodhound Buddy has gone missing, yet unbeknownst to them Buddy was an agent tasked with ensuring Dr. Charles Brody completes his research into finding a cure for the allergy to dogs, and was in fact captured by enemy cats. When fellow agent, Anatolian Shepherd Butch, reports Buddy's capture to his superiors, canine agents are dispatched to help ensure Dr. Brody completes his research.
One month later, Brody's wife Carolyn goes to adopt one of a litter of Beagle puppies. A Doberman Pinscher agent replaces the litter with a pack of Miniature Pinscher agents, failing to notice the youngest Beagle left behind. Carolyn adopts the Beagle puppy and names him Lou after her son, Scotty, sarcastically suggests the name 'Loser'. Scotty is immediately dismissive of Lou as he still believes Buddy might come back, when in fact he has escaped capture and retired to Boca Raton. After saving Lou from an explosive trap laid by cats, 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 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.
The leader of the cats, Persian cat Mr. Tinkles, plans to exploit Dr. Brody's research as part of a plan to conquer the world. 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. When Dr. Brody believes he is on course to a breakthrough, Mr. Tinkles contracts a Russian Blue mercenary named Dimitri Kennelkoff to destroy the research. Kennelkoff battles Lou and Butch, damaging the Brodys' house and attempts to blow up Dr. Brody's laboratory, but Butch disables the bomb and captures Kennelkoff.
Lou makes an attempt to bond with Scotty, who is reluctant but eventually plays with Lou, but in doing so they accidentally wreck his father's lab and ruin all his research. However, doing so inadvertently results in the creation of the formula which cures human allergies to dogs. Learning of this, Mr. Tinkles sets a trap for the Brodys by luring them out with fake tickets to a soccer game. The dogs subsequently receive a video from Mr. Tinkles demanding the research as a ransom for the family. When an assembly of dogs decide not to surrender the research, Lou angrily disobeys them and Butch and agrees to exchange the formula with Mr. Tinkles for the Brodys; however, the cats double-cross him.
The rest of the dogs track down Mr. Tinkles to his owner's Christmas tree flocking plant, where they learn that he has reversed the formula to give people an allergy to dogs, and plans to use mice to spread the mass-produced allergy all over the world. 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 in an explosion which destroys the whole factory; Butch rescues Lou and tearfully admits that Lou was right to love his adoptive family. Lou is joyfully reunited with Scotty and the Brodys and decides to live normal dog's life with the Brodys until he can serve as a full-grown agent. Meanwhile, Mr. Tinkles is sent to live with his owner's maid Sophie and her three sisters, who dress him in increasingly humiliating outfits as retribution.
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