Charlie B. Barkin (Burt Reynolds), a rascally German Shepherd with a shady past, breaks out of the New Orleans Dog Pound with the help of his faithful friend Itchy (Dom De Luise), a nervously hyperactive dachshund. He then makes tracks to reunite with his gambling casino partner Carface Malone (Vic Tayback), a shifty pitbull who has planned a dastardly, and potentially deadly, double cross.

Suddenly, Charlie finds himself at the Pearly Gates, face to face with the Heavenly Whippet (Melba Moore). Itchy wants revenge for the betrayal before he can enter heaven and befriends a little girl named Anne-Marie who can talk to animals, and help him in his quest. After a series of fiendish schemes, close scrapes and unexpected adventures, both Charlie and Anne Marie find their lives at stake. Only one can be saved and the outcome is in Charlie's paws...