Pongo is a Dalmatian who lives in a London bachelor flat with his owner named Roger Radcliffe, a romantic songwriter and his new friends, Ian Isberto, Dexter, Cyborg, Buttercup, Gohan. Bored with bachelor life, Pongo decides to find a wife for Roger and a mate for himself. While watching various female dog-human pairs out the window, them spots the perfect couple, a woman named Anita and her female dalmatian, Perdita. Them quickly gets Roger, Ian and Friends out of the house and drags them through the park to arrange a meeting. Pongo accidentally causes both Roger and Anita to fall into a pond, but it works out well as the couple falls in love. Both the human couple and the dog couple marry. Team Isberto are now their Chaperones.
Later, Perdita gives birth to 15 puppies. One almost dies, but Roger, Ian and the others were able to revive it by rubbing it in a towel (because of which, they would name the pup, "Lucky"). That same night, they are visited by Cruella De Vil, a wealthy former schoolmate of Anita's. She offers to buy the entire litter of puppies for a large sum, but Roger, Ian and the others says they are not selling any of the puppies. Weeks later, she hires Jasper and Horace Badun to steal all of the puppies. Ian and Dexter were also stolen at the same time. When Scotland Yard is unable to prove she stole them or find the puppies and their friends, Cyborg, Buttercup, Gohan, Pongo and Perdita use the "Twilight Bark", normally a canine gossip line, to ask for help from the other dogs in England. In a subplot, Horace and Jasper realized that they also captured Ian and Dexter with the puppies and they locked the two heroes in a room. In that room, they were confronted by Mojo Jojo, Mandark, Cell 18, Smithy, and Le Quack. They all told the two good guys that they were sent by Ganondorf to join forces with Cruella and told them their evil plan to Make Dalmatian Fur Coats and they told them that they cannot interfere.
Meanwhile. Colonel, an old sheepdog, along with his compatriots Captain, a gray horse, and Sergeant Tibbs, a tabby cat, find the puppies, Ian, and Dexter in a place called Hell Hall (A.K.A The De Vil Place), along with other Dalmatian puppies that Cruella had purchased from various dog stores. Tibbs learns the puppies are going to be made into dog-skin fur coats and the Colonel quickly sends word back to London. Upon receiving the message, Cyborg, Buttercup, Gohan Pongo and Perdita immediately leave London to retrieve their puppies and their friends. Meanwhile, Tibbs overhears Cruella ordering the Baduns and the villains to kill and render the puppies that night out of fear the police will soon find them. In response, Tibbs attempts to rescue the puppies, Ian and Dexter himself while the Baduns and the villains are watching the television, but they finish their show and come for them before Tibbs can get the puppies, Ian and Dexter out of the house. Cyborg, Buttercup, Gohan, Pongo and Perdita burst through a window just as the Baduns and the villains have cornered them and are about to kill them. While the adult dogs attack the two men and the three good guys attack the villains, Colonel and Tibbs guide the puppies, Ian and Dexter from the house. After a happy reunion with their own puppies, Everyone realize there are 84 other puppies with them. shocked at Cruella and the Villains plans as they are part of One of Ganondorf's dastardly plots to get rid of Team Isberto, they decide to adopt all of the puppies, certain that Roger and Anita would never reject them. The dogs and our heroes begin making their way back to London, aided by other animals along the way, with Cruella, the Baduns, and the villains giving chase. In one town named dinsford, they cover themselves with soot so they appear to be labrador retrievers, then pile inside a moving van going back to London. As the van is leaving, melting snow clears off the soot and Cruella sees them. In a maniacal rage, she follows the van in her car. Around the same time, Mojo Jojo, Mandark, Smithy, Cell 18 and Le Quack appear and Team Isberto decided to fight them. Mojo fought Buttercup but he got punched out and yells "Curses!", Dexter and Mandark fight until Dexter defeated Mandark, Cyborg blasted Smithy away, and Gohan defeated Cell 18. After the battle, our heroes saw Cruella driving up to the van and rams it, but the Baduns, trying to cut off the van from above, and Le Quack coming from a different direction, end up colliding with her. Both vehicles crash into a deep ravine. Cruella yells in frustration as the van drives away. The Police found Le Quack and was sent to jail.
Back in London, Roger and Anita are attempting to celebrate Christmas and Roger's first big hit, a song about Cruella, but they miss their canine friends and their Chaperones. Suddenly barking is heard outside and after their nanny opens the door, the house is filled with dogs. Team Isberto gave Anita and Roger the christmas surprise after wiping away more of the soot, the couple and his friends is delighted to realize their companions have returned home. They decide to use the money from the song and the reward to buy a large house in the country so they can keep all 101 Dalmatians. The movie ended with a very prolonged search. Le Quack was not held for long, however, and after destroying the car and stealing a police uniform, he swore revenge on Team Isberto.