Sonic and friends along with Natsumi and Fuyuki and Keroro are in London as they are visiting their uncle (from their father's side) and his pet dalamatian Pongo. Bored with bachelor life, Pongo decides to find a wife for Roger and a mate for himself with help of Sonic and friends. While watching various female dog-human pairs out the window, he spots the perfect couple, a woman named Anita and her female dalmatian, Perdita. He quickly gets Roger out of the house and drags him 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.
Several weeks later, Roger and Anita are visited by Cruella De Vil, Anita's old schoolmate; and Perdita has a litter of 15 puppies. One night as Roger, Anita, Pongo, Perdita were out along with Sonic, Oswald, Auqa, Sakura, Natsumi, Bugs Bunny and Shadow. Leaving Daffy, Roger, Koyuki, Fuyuki, Keroro, Tom, Slyvester, Jerry and Dororo to watch the puppies. Unfortnatly, Horace, Jasper and the Weasels (From Sonic's Adventures of Who Framed Roger Rabbit) are near by and trap the nanny in the attic as they manage to kidnap the puppies along with Daffy and some of the other. When Sonic and other how no idea were their friends and the puppies are, so Pongo and Perdita sound the Twilight bark, normally a canine gossip line, to ask for help from the other dogs in England.
Colonel, an old sheepdog, along with his compatriots Captain, a gray horse, and Sergeant Tibbs, a tabby cat, find the puppies in a place called Hell Hall (A.K.A The De Vil Place), along with other Dalmatian puppies and Sonic's friends are located. Tibbs learns the puppies are going to be made into dog-skin coats and the Colonel quickly sends word back to London. Upon receiving the message, Pongo and Perdita immediately leave London to retrieve their puppies. Meanwhile, Tibbs overhears Cruella ordering the Baduns 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 with the help of Tom, Jerry, Slyvester, Dororo and Keroro, while the Baduns and The Weasels are watching the television, but they finish their show and come for them before Tibbs can get the puppies out of the house. Pongo and Perdita and Sonic and accompany burst through a window just as the Baduns and Weasels have cornered them and are about to kill them. While the others attack the goons, Colonel and Tibbs guide the puppies and our heroes from the house.
After a happy reunion with their own puppies, the Pongos realize there are 84 other puppies with them. shocked at Cruella's plans, 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 and the Baduns and The Weasels giving chase. In one town, they cover themselves with soot so they appear to be labrador retrievers,and Tom looks like a Black cat, 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 and rams it, but the Baduns, trying to cut off the van from above, end up colliding with her. Both vehicles crash into a deep ravine. Cruella yells in frustration as the van drives away.
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. Suddenly barking is heard outside and after their nanny opens the door, the house is filled with dogs and animals and four girl and one boy covered in dirt. After wiping away more of the soot, the couple is delighted to realize their companions have returned home. They decide to use the money from the song to buy a large house in the country so they can keep all 101 Dalmatians.
- Guest Starring Tom, Jerry, Bugs Bunny, Sylvester, Tweety, Natsumi, Fuyuki and Keroro
- The Weasel from "Who Framed Roger Rabbit" work for Cruella, along with Rocky and Mugsy from the Looney Tunes since Daffy, Bugs, Slyvester and Tweety had past experince with them
- DisneyDaniael93's Pooh's Adventures of 101 Dalamatians was inspiration for this film
- Sergeant Tibbs will join Sonic's team at the end of this adventure.