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As the movie begins, Annabelle, the head angel in Heaven, begins to tell a litter of puppy angels the story of how Charlie B. Barkin and Itchy Itchiford saved Christmas in San Francisco from her evil cousin, Belladonna (or, as the puppies call her, the "Boogie Dog").
The story begins on Christmas Eve, and in the outdoor bar run by Charlie's confidante Sasha, he, Itchy, and the rest of their gang celebrate the night before Christmas with a litter of homeless stray puppies, and all the while, attempt to earn enough money for a lame puppy named Timmy, who needs an operation to cure his leg. However, Carface Caruthers and his not-too-bright sidekick, Killer, are not into celebrating the holidays. The former has come to collect his loans back—with excessive interest (e.g. he demands Sasha give him ten bones, though she had borrowed four, meaning he wanted 150% interest). And, as he told them, he intends to claim what's his, and using a hypnotic dog whistle created by Belladonna, he robs the party of their valuables—and the donations meant for Timmy's operation. Speaking of which, Sasha eventually walks him to his owner, Martha, who then picks him up, thanks her, and then takes him in to re-bandage his leg.
After several failed attempts to claim the whistle, the angels discover that Carface is working with Belladonna to ruin Christmas for all, by building a king-sized version of the whistle that, at the stroke of midnight ushering in Christmas Day, will hypnotize every dog in San Francisco to steal their masters' presents. Also, they've discovered that Carface has made a deal with Belladonna: he gets all the presents, and she gets to destroy Christmas for everyone.
Later, Charlie and Itchy are alerted by Annabelle to save Christmas, as it will be their most important mission yet. And to aid them toward their success, she provides them with a "Miracle Dog Tag", but she warns them that it won't locate the whistle, so they decide to use its magic to attempt to change Carface's mind about ruining Christmas. To that end, a take on A Christmas Carol follows suit.
Later that night, Carface is getting ready for bed so he'll be rested for Belladonna's world domination plan, but is unable to fall asleep, so he turns on the TV and discovers that a Christmas show called It's A Wonderful Carface is playing. The narrator, who is Charlie in disguise, warns him that he will be visited by three spirits, and each of them will arrive at the sound of a bell. He turns the TV off, berating the warning, until the town clock begins to chime, and Itchy appears as the Ghost of Christmas Past. He takes Carface into the past, and he remembers how much his human owner loved him—until he was thrown out of their home. From then on, he was convinced that humans were completely untrustworthy and organized a crime syndicate.
Then, the Ghost of Christmas Present (played by Sasha) shows Carface two events: first, how Killer celebrates Christmas (he's gotten his boss a new Swiss army knife for Christmas), and then, a scene at Timmy's home and the fun he has with Martha. She even shows that they would do anything for each other—but he would rather do the right thing and tell the truth, because when they were playing, a priceless china plate her mom treasured got broken, and she tried to cover up for him, but he wouldn't let her be blamed for his mistake, so he whined, indicating that he had broken it. Carface thought he would be thrown out of there, but instead, her mom commended him for telling the truth. As he watched the scene, Carface hadn't realized that Timmy was in such bad shape, until Sasha told him that if Timmy did not get the operation he desperately needed, he would not live to see next Christmas.
After that visit, Carface decides to loosen himself up by reading the comics in the newspaper, but later on, he starts stiffening up again when he does so, and as another bell rings throughout the room, he is taken into another world, where he meets the Ghost of Christmas Future, who, during a Gospel-style song-and-dance number of "Clean Up Your Act," turns out to be Charlie. He shows Carface that Timmy is about to fall under the spell of the whistle, and at the stroke of midnight, he becomes hypnotized and begins to walk out with Martha's Christmas present. Carface tries to snap him out of his trance, but, since he's impossible to see, hear, or feel to others in the future, he is unable to stop him as he walks through the doggy door and is never seen again.
On this note, Carface decides that Belladonna's plan must be stopped, but not before she herself takes him and Killer to Alcatraz Island, where the whistle has been built. Everything goes as planned at first, but then Carface remembers Timmy and Martha. He knew that if Timmy fell under its spell, he might never see another Christmas. After his first attempt to shut it down fails (Belladonna melts the on/off switch), he attempts to short-circuit it Ben Franklin–style, by climbing up the kite string feeding power to it from Belladonna's lightning storm and interrupting the electricity flow. It is destroyed and the dogs of San Francisco are freed from its hypnotic influence.
Belladonna demands to know why the whistle was destroyed, and, to Killer's surprise, Carface accepted full responsibility for thwarting her plan. She attempts to destroy them, until Annabelle intervenes and buries her in a snowbank. Carface thanks her for her help, but she tells him he did all of the work. Killer feels like giving Annabelle and Carface a group hug, though the latter threateningly disagrees. Annabelle then sends them back, and says, "Oh, and good work." (It is unknown whether she said it to them or the audience.)
On Christmas morning, Carface shows up wearing a Santa suit and returns all the valuables he stole the previous day, and even volunteers to donate money toward Timmy's leg operation. The movie ends with a gentle snowfall in San Francisco, the reprise of "When We Hear a Christmas Carol", and, back to where Annabelle has been telling the story to the angel puppies in Heaven, a wish for a Merry Christmas from Charlie, Itchy, and Annabelle (and the angel puppies) to all viewers.
- "When We Hear a Christmas Carol"
- "I Always Get Emotional at Christmas Time"
- "Clean Up Your Act"
- Ernest Borgnine - Carface Caruthers, the bulldog and, as unusual, the protagonist.
- Steven Weber - Charlie B. Barkin, the German Shepherd/Ghost of Christmas Future. He is usually the protagonist, but this time, he's the deuteragonist.
- Dom DeLuise - Itchy Itchiford (the dachshund), Charlie's best friend/Ghost of Christmas Past. He is usually the deuteragonist, but this time, he's the tritagonist.
- Sheena Easton - Sasha La Fleur (the Irish Setter), Charlie's on-again, off-again girlfriend/Ghost of Christmas Present. She is the tetartagonist.
- Charles Nelson Reilly - Killer the schnoodle, Carface's partner-in-crime as well as best friend.
- Bebe Neuwirth - Annabelle, an angelic whippet who welcomes dogs into Heaven/Belladonna, her evil cousin who plans to ruin Christmas. She is the main antagonist of the film.
- Beth Anderson - Martha, young human girl who lived with her mother and takes care of Timmy.
- Taylor Epperson - Timmy, a crippled puppy who nevertheless doesn't complain about it. He is Martha's pet.