A thousand years ago, dogs were free to roam as they pleased. However, the cat-supremacist Kobayashi Dynasty declared war on dogs, seeking to eradicate them. A child warrior sympathetic towards the threatened dogs
decapitated the head of the Kobayashi Clan, ending the war, and was immortalized as the Boy Samurai of Legend. In 2038, an outbreak of
canine flu spreads throughout the
Japanese city of Megasaki. The city's
authoritarian mayor, Kenji Kobayashi, ratifies an official decree banishing all dogs to Trash Island, despite the insistence of Professor Watanabe, the mayor's political opponent, that he is close to creating a cure. The first deported canine is a white and black-spotted male dog named Spots Kobayashi, who served as the
bodyguard of 12-year-old
orphan Atari Kobayashi, the mayor's distant nephew and
ward. Six months later, Atari hijacks a plane and flies it to Trash Island, now nicknamed "the Isle of Dogs", to search for Spots. After crash-landing, Atari is rescued by a dog pack ostensibly led by an all-black canine named Chief, a lifelong stray, along with Rex, Boss, Duke, and King. With their help, Atari finds a locked cage that apparently contains Spots' skeleton, but they realize it is not him. They then fend off a rescue team sent by Mayor Kobayashi to retrieve Atari. Chief initially declines to continue helping Atari, but is convinced by Nutmeg, a female ex-
show dog whom Chief is smitten with. The pack seeks advice from sage-like dogs Jupiter and Oracle, who surmise that Spots might be held captive by an isolated tribe of dogs rumored to be
cannibals. Meanwhile, Watanabe finally develops a successful serum and shows the results to Kobayashi, who merely dismisses him. By order of the mayor's
hatchet man Major Domo, the professor is placed under
house arrest and assassinated with poisoned
sushi. Tracy Walker, an
American exchange student, member of a pro-dog activist group and Nutmeg's owner, suspects a conspiracy and begins to investigate, in the process developing feelings for Atari. Kobayashi and his political party are revealed to be responsible for the dog flu outbreak and aim to succeed at exterminating dogs where Kobayashi's ancestors failed. During their journey to the dog tribe, Chief and Atari are separated from the others. Atari gives Chief a bath, revealing his white and black-spotted coat and thus his striking resemblance to Spots. The two bond and rejoin the rest of the pack. Another rescue team attacks them, but they are saved by Spots and the dog tribe. Spots confirms that he is Chief's older brother and that he was rescued by the tribe, who were test subjects from an abandoned secret lab. Spots became their leader and mated with a female tribe member named Peppermint, who is pregnant with their first litter. Because of these new responsibilities, Spots requests Atari replace him as his bodyguard with Chief; initially hesitant, both he and Atari accept. Word reaches the dog tribe that Kobayashi plans to
euthanize all dogs with poison gas; Atari and the dogs build boats to return to Megasaki. Meanwhile, Tracy confronts Watanabe's colleague Yoko Ono, who confirms Tracy's conspiracy theories and gives her the last vial of serum. At his re-election ceremony, Kobayashi prepares to give the extermination order when Tracy and the activist group interrupt, presenting evidence of his corruption. Kobayashi proceeds to deport Tracy, but before he can do so, Atari and the dogs arrive. They confirm that the serum works by testing it on Chief, curing him. Atari addresses the crowd and recites a
haiku he wrote and dedicated to Kobayashi, rekindling the sympathy that once existed between dogs and humans. Touched by Atari's words, Kobayashi officially repeals the dog banishment decree. Enraged, Major Domo tries to initiate the extermination himself, but his plans are thwarted by the dogs and the activist group. In the chaos, Atari and Spots are wounded and taken to a hospital, where Kobayashi donates one of his
kidneys to save his nephew. Atari becomes the new mayor of Megasaki after Kobayashi's crimes render him ineligible to hold office. One month later, Atari has had all dogs reintegrated into society and cured of the dog flu, while Kobayashi, Major Domo, and their co-conspirators are sent to jail. Chief's pack dogs are all back with their owners: Boss returns to being the mascot of the Dragons' baseball team (inferred that the coach owns him), King has returned to being a dog food commercial star and lives with a couple with their 3 children and has a big supply of dog food and puppy snaps, Duke lives with a large family who is seen watching one of King's commercials on TV, and Rex is owned by an elderly female librarian and is shown by her in the library with his own thick mat. Atari and Tracy become a couple, while Chief and Nutmeg become their bodyguard dogs. Meanwhile, Spots, having survived his injuries, raises his litter with Peppermint under the care of a
Shinto priest. ==Cast==