The film tells the story of Patch, the loneliest dalmatian, who felt "lost in a sea of spots" until he met his TV hero Thunderbolt. Unlike several Disney direct-to-video sequels that essentially retell the original film's story (such as The Little Mermaid II: Return to the Sea), it takes characters from the original film in some new directions.
In the film, Patch was accidentally left behind after the Radcliffes moved to Dalmatian Plantation located at Cherry Tree Farm, Little Devon. Patch becomes a part of Thunderbolt's TV show and wants to know: is he one of a kind, or just one of 101? Now is his opportunity as Thunderbolt thinks he will be replaced when it is just a plot by his sidekick, Lil' Lightning, to make him quit once and for all and make a jealous Lightning the star. Patch becomes heartbroken when he finds out that his favorite wonder dog is just a TV actor.
Roger and Anita Radcliffe, and their canine clan are packing for the big move to Dalmatian Plantation, a home in the country with plenty of room for the 101 puppies and far from the clutches of Cruella De Vil. The feistiest puppy, Patch, feels lost in a sea of spots and longs to be a one-of-a-kind wonder dog like his TV hero, Thunderbolt. While watching the The Thunderbolt Adventure Hour he hears about a chance to appear on the show while it is bring filmed in London. However, the move will interfere with his opportunity - until he's accidentally left behind in the commotion. He heads for the audition to meet his hero. Meanwhile, Thunderbolt's "trusty" sidekick, Lil' Lightning, tells him the producers want to replace him with a younger dog. In order to save his job, he decides he will go into the real world and perform an act of true heroism to prove himself. A veritable reference book to Thunderbolt's many adventures, Patch provides the perfect guide for him in his attempts at real-life heroics.
Meanwhile, Cruella is back and more obsessed with dalmatians than ever. At first, she is able to calm her frenzy through an affiliation with a spot-fixated German artist named Lars. Meanwhile, Thunderbolt makes several attempts at "heroism", telling Patch he is giving him a "Junior Deputy Test" and will let him be on the show if he can pass. This "test" involves him unwittingly giving instructions on how Thunderbolt, who has no idea how to act without a script, should save the day. Back at his trailer, Lightning's true nature is revealed. Fed up with being second best, he cons the producer, who is both desperate and frantic over Thunderbolt going missing, into recasting him as the hero. Cruella soon discovers that Lars, despite his best efforts, is unable to recreate the look she desires.
In order to inspire him, she begins hunting for the dalmatian puppies, but is angry to find Anita's house empty. However, using a newspaper picture of Patch at the audition, she reads their new address off his ID tag. Meanwhile, he and Thunderbolt bond over their mutual fear of being "just another dog" and Thunderbolt begins teaching him how to bark properly. The Radcliffes finally become aware that he is missing as Cruella posts bail for her former cronies, Jasper and Horace, and sends them to the farm to steal the remaining 98 puppies by locking them in a stolen Kanine Krunchies truck. Lars becomes enamored with them and is inspired to paint, but Cruella announces that he going to make a masterpiece out of puppy fur. HE refuses, but she simply ties him up and goes back to her original plan of making a puppy fur coat.
The imprisoned puppies use the Twilight Bark to send an SOS, which is picked up by Patch and Thunderbolt, and they set out to save Patch's family. Lightning is horrified when he discovers Thunderbolt might actually become a hero and hurries to the warehouse where the puppies are being held. He convinces Thunderbolt not to use Patch's stealth plan, but to openly attack. However Cruella shows up and locks them in a cage. Lightning sneaks in and reveals that Thunderbolt is a fraud. Poor Patch is deeply hurt that Thunderbolt would lie, but soon realizes that their current situation was covered in one of the TV episodes and manages to escape. He releases his family, but Thunderbolt stays in his open cage. Jasper and Horace confess to Cruella the puppies are missing, but Patch tricks them into going downstairs while the dogs escape via the roof and get onto a double decker bus, which they accidentally start.
Cruella follows in hot pursuit as they race through the streets of London, crashing through the filming of the new "Lil' Lightning" show. She finally corners the puppies in an alley. Patch tries to hold off the trio as the others escape, but they are undaunted. Luckily, Thunderbolt arrives (having hitched a lift with Lars) and apologizes to Patch, saying he is not a hero, but he can act like one. He fakes a heart attack, distracting Cruella (and managing to have her knock out Jasper and Horace) while the puppies escape before collapsing. Patch puts the bus into reverse, forcing the four bad guys into the Thames River.
Patch and Thunderbolt survey the scene, both letting out deep, heroic barks. Lightning is arrested, along with Jasper and Horace, while Cruella, who has now driven completely insane, is sent to a mental institute. Pongo and Perdita arrive and tell Patch how proud they are of him. Thunderbolt confesses that he is just an actor, but Patch is "a real, one-of-a-kind wonder dog." A newspaper montage reveals the characters' fates: Lars, using a painting Patch accidentally made by throwing paint at Jasper and Horace, finally receives credit for his "genius"; Jasper and Horace open up a ladies' boutique with the motto: "Fur Bad, Nylon Good"; Roger's new song, "Seeing Spots", becomes a smash hit and Cruella is featured in an issue of "The Institution". A post-credits scene shows Thunderbolt, with his new sidekick Patch, in his TV show, with the other puppies serving as extras.
- Bobby Lockwood as Patch: The main character, a small dalmatian puppy with a large black patch over one of his eyes; hence his name. He feels lonely and left-out oftentimes with his family, thinking that he is just one of the famous 101 dalmatians, and longs for a chance to become separate and leave the shadow of his brothers and sisters. He is a good pup, very adventurous, bold, and strong-minded. He quickly befriends Thunderbolt, the famous TV wonder dog whom he adores.
- Barry Bostwick as Thunderbolt: As the movie opens, it is shown that Thunderbolt is not exactly bright, and very self-centered and rude to his sidekick, Lil' Lightning, which eventually provokes the Corgi to revolt. When Thunderbolt runs away, tricked by Lightning that the director of his famous show plans to kill him off, he runs into Patch, and the two quickly bond, trying to do heroic feats to prove that Thunderbolt is a real hero. As the film progresses, Thunderbolt becomes a father like figure to Patch, and loses his starry-eyed, naive ways to become a strong, brave, and faithful dog. Thunderbolt is a German Shepherd and his sidekick, Lil' Lightning, is a Pembroke Welsh Corgi.
- Jason Alexander as Lil' Lightning: The Welsh Corgi of Thunderbolt's famous show. He is initially portrayed as Thunderbolt's little sidekick. Eventually, he becomes angry at always crawling in Thunderbolt's shadow, and tricks him into running away, then plots to manipulate the director into rewriting the show slanted towards Lightning. When Thunderbolt and Patch return, endangering Lightning's chance at fame, he reveals himself to be the traitor he is and has the two dogs locked away. In the end, however, he is overpowered and taken away by the pound. He starts off being a neutral character, but later becomes an antagonist in the film.
- Susanne Blakeslee as Cruella De Vil: The villain of the original film, back once again to kidnap the puppies. Naturally, she serves as a major antagonist.
- Martin Short as Lars: A stylish but rather strange artist who loves nothing more than painting spots. It is suggested he had some romantic feelings towards Cruella, but when she captures the dalmatian puppies again and plans to break her rules of goodness and make coats out of them, he rebels, only to be tied up.
- Samuel West as Pongo: Father (and adopted father) of the 99 Dalmatian puppies, he is loving but distracted, something here that forces Patch to feel lonely and just one-hundred and one, instead of standing out.
- Kath Soucie as Perdita: Mother (and adopted mother) of the 99 Dalmatian puppies, Perdita is a gentle, loving soul who only wants the best for her children (and adopted children), and is horrified to find her children missing once again.
- Tara Strong as Two-Tone: One of Patch's 98 siblings.
- Kasha Kropinski as Penny: Another of Patch's 98 siblings.
- Maurice LaMarche and Jeff Bennett as Jasper and Horace: Cruella's two bumbling henchmen.
- Mary MacLeod as Nanny
Rotten Tomatoes rating for the film is currently 60% "fresh" based on 5 reviews and with a 4.8 rating, but without a consensus.
- A video game of the film was made for the PlayStation. It was released October 21, 2003. it has 1 review, a 3/5, calling it hard to play and repetitive.
- The 1990 Walt Disney Pictures logo has been customized for the film; dog barks were heard in the background as the music plays.
- This is the first part of the franchise in which Lucky is voiced by an actual male (Ben Tibbet), as normally he is voiced by a female (Mimi Gibson in the first film, Russi Taylor in the animated storybook, and Pamela Segall-Adlon and Debi Mae West in the TV series).