In 1939 Louisiana, a dachshund named Itchy helps his dog friend, Charlie, escape from the pound. Charlie seeks out his business partner, a corrupt bulldog named Carface, at their casino on an abandoned ship on the edge of a bayou. Although Carface pretends to welcome him back, he tells Killer, his neurotic assistant, that Charlie must die. After a celebratory dinner held by Carface, a drunken Charlie is dragged to the edge of a dock, blindfolded, and run over by an unmanned automobile. Charlie drowns and goes to heaven, where a whippet angel shows him a stopped pocket watch that represents his lifespan. Although Charlie is not ready to die, the angel tells him no one is ever allowed to return to Earth. Learning there are no surprises in heaven, Charlie sings about his desire for surprise and dances with the angel to distract her, then steals his “life watch” and winds it backward, plummeting back to Earth. With the life watch around his neck, Charlie finds Itchy, who thinks his friend is a ghost and tries to run away. Assuring Itchy he is still alive, Charlie announces plans to take revenge against Carface. Itchy tries to discourage him by insisting that Carface keeps a monster in “the basement” of the ship. The dogs crawl into an airshaft to spy on the monster, and discover a little girl dressed in rags. They watch as Carface pays a visit, urging the girl to converse with a caged rat. The girl, Anne-Marie, addresses the rat as “Mr. Longtail” and asks which rat will win the race at the casino that night. Once she relays the predicted winner, Carface orders Killer to change the odds and leaves Anne-Marie trapped in the room despite his promise to let her outside. Recognizing the girl’s ability to talk to animals as a business opportunity, Charlie approaches and learns she is an orphan. Quickly gaining her trust, he and Itchy steal her away. When Carface realizes the girl is gone, he rages at Killer and demands her return. Charlie takes Anne-Marie home with him to an old taxicab in a junkyard. He reads her a bedtime story and reluctantly obliges her request for a goodnight kiss. She keeps him awake by tossing and turning, then praying out loud for a mommy and daddy. Anne-Marie asks Charlie to help her find parents, and he agrees as long as she goes to sleep. The next day, Itchy and Charlie take Anne-Marie to a race track and ask her to speak to the horses. She accuses Charlie of acting just like Carface, but he promises they will donate their winnings to the poor and use it to buy her new clothes so she can attract parents. A horse named Stella tells Anne-Marie that a notoriously slow horse, the Grand Chawhee, will win because it is his birthday. Using Itchy as a decoy, Charlie steals a young man’s wallet for betting money. The man’s wife takes an interest in Anne-Marie, asking about her parents, but the orphan rushes off with her canine friends. To place a bet, Anne-Marie stands on top of Itchy and Charlie under a large coat and pretends to be a man. Grand Chawhee’s odds are 1000 to 1, but the other horses allow him to win for his birthday, as planned. Over time, Itchy and Charlie use Anne-Marie to win more money at various events, including turtle races and kangaroo boxing matches. She disapproves when Charlie and Itchy open a new casino and threatens to leave, but Charlie takes her with him to distribute food to the poor. At the home of his friend, Flo, Charlie delivers several pizzas to her puppies, who call him “Uncle Charlie.” Carface learns about Charlie’s re-emergence and new casino and plots his murder, for which Killer procures an atomic ray gun. Meanwhile, Charlie sings a song to Flo’s puppies to encourage sharing and presents them with a cake. When Anne-Marie discovers the wallet Charlie stole, she finds a picture of the couple inside and imagines life with the two of them as her parents. That night, Charlie has a nightmare that he is sent to hell after his life clock stops. When he awakens, Anne-Marie is gone, and the puppies inform him that she went to return the stolen wallet. At the home of the couple, Harold and Kate, Anne-Marie enjoys breakfast and explains that she lives with Charlie in a junkyard. Kate pulls Harold aside and insists they keep the girl, while Charlie appears at the window and tells Anne-Marie she is the best friend he ever had. Unable to part ways with the dog, Anne-Marie escapes out the window. Shortly after, Carface and Killer pursue Charlie and Anne-Marie with the ray gun. However, when Charlie is shot, he remains alive because his life clock is still ticking. Charlie and Anne-Marie reach a hideout but fall through a hole in the floor and drop into the bayou, where a tribe of rodents takes them captive. Their leader, a large alligator named King Gator, arrives and begins to eat Charlie but stops when he hears the dog’s howl. Declaring that Charlie has a lovely singing voice, King Gator suggests they perform a duet, and the two sing “Let’s Make Music Together.” Later, a wounded Itchy finds Charlie and says he was beaten by Carface and his thugs, who also burned down their casino. Itchy begs Charlie to leave town with him and accuses him of being in love with Anne-Marie. Charlie denies it, saying he was only pretending to be her friend. The girl overhears and runs away in tears, leaving her stuffed bunny behind, and Carface kidnaps her once again. Flo finds the stuffed bunny and tells Itchy to take it to 402 Maple Street, where Harold and Kate live. Waking up to the sound of dogs barking on their front porch, Harold and Kate open the door to find a pack of dogs led by Itchy, who carries Anne-Marie’s bunny in his mouth. Meanwhile, Carface’s thugs catch Charlie, tie him to an anchor, and throw him into the bayou. King Gator hears his cry and comes to the rescue, releasing Charlie. Kate and Harold follow Itchy and his friends to Carface’s casino, where Anne-Marie has fallen into the bayou in the middle of a fiery gasoline spill. Charlie dives into the water to save her and, in the process, loses his life watch. As the hands of the watch come to a stop, he places Anne-Marie on a floating cargo box, then drowns. Killer pushes Anne-Marie to shore, where Harold and Kate await her. Sometime later, Itchy joins Anne-Marie in bed in their new home at Harold and Kate’s. Charlie’s ghost emerges from an ominous red cloud and apologizes to a sleeping Anne-Marie. Just then, a white orb of light appears, banishing the red dragon that awaited his doomed soul. The whippet angel calls out to Charlie, announcing he has earned back his place in heaven. Before he floats away, Anne-Marie wakes up and shares a tearful goodbye with Charlie. Later, Carface arrives in heaven and, like Charlie once did, ignores the whippet angel by stealing his life watch, turning it back, and plummeting back to Earth.