Charlie, the heroic, roguish mutt of All Dogs Go To Heaven, is growing impatient with the predictability of Dog Heaven, and decides he'd rather be back amongst the living. He gets his wish when the nefarious Carface sends him and his buddy Itchy back to Earth to retrieve Gabriel's horn--which Carface tried to steal.
While in San Francisco, the dogs become engaged in numerous misadventures, and Charlie falls head over paws for Sasha, a lovely Irish setter. But in their quest for the coveted trumpet, Charlie and Itchy encounter a devilish cat named Red who also wants the horn--as part of a heinous plot to lock up all dogs permanently.