On Fifth Avenue, an orphaned kitten named Oliver is left abandoned after his fellow orphaned kittens are adopted by passersby. Wandering the streets by himself in search of someone to adopt him, he meets our heroes and a laid-back dog named Dodger who assists him in stealing food from a hot dog vendor named Louie. Dodger then flees the scene without sharing his bounty with Oliver. Oliver follows Dodger all throughout the streets until he eventually arrives at the barge of his owner, a pickpocket named Fagin, along with his meal, to give to his friends: Tito the chihuahua, Einstein the Great Dane, Rita the Afghan Hound, and Francis the bulldog. Oliver sneaks inside, located below the docks, and is discovered by the dogs. After a moment of confusion, he is then received with a warm welcome. Fagin comes in and explains that he is running out of time to repay the money he borrowed from Bill Sykes, a nefarious shipyard agent and loan shark. Sykes tells Fagin it must be paid in three days, or else. Sykes' dobermans, Roscoe and DeSoto, attack Oliver but he is defended by Fagin's dogs. Immediately thereafter, a depressed Fagin returns to the barge, lamenting that he only has three days to find the money. After the dogs cheer him up, he is introduced to Oliver, and, considering that they all need help, accepts him into the gang.
The next day, Fagin and his dogs, now including Oliver (and our heroes), hit the streets to sell some shoddy goods and perhaps steal money. Oliver and Tito attempt to sabotage a limousine but the plan fails when Oliver accidentally starts it, electrocuting Tito, and he is caught and taken home by its passenger, Jennifer "Jenny" Foxworth, and her butler, Winston. Her parents are out of town and she adopts Oliver out of loneliness. Georgette, her pompous and pampered poodle, is enraged and jealous of his presence and wants him removed from the household. Our heroes, Dodger, and the others manage to steal him from the Foxworth family and bring him back to the barge. He explains that he was treated kindly and did not want to leave, much to the shock of Dodger who feels that he is being ungrateful, but allows him the opportunity to leave. However, Fagin arrives, concocts a plan to ransom him, and sends Jenny a ransom note. She discovers it and sets out to get him back. Meanwhile, Fagin tells Sykes of his plan, who says he is proud of him for "starting to think big".
Later, Jenny meets up with Fagin, who is surprised that the "very rich pet owner" is only a little girl. Bothered by his conscience after seeing her distraught over losing Oliver, he returns him freely. Just then, Sykes comes out of the shadows and kidnaps her, intending to ransom her and declaring Fagin's debt paid.
Dodger rallies Oliver and the other dogs to rescue Jenny from Sykes, but are confronted by Sykes, Roscoe, and DeSoto after they free her. Fagin saves them with his scooter and a chase ensues into the subway tunnels. Jenny is pushed onto the hood of Sykes's car, where she holds onto the hood ornament, and Oliver and Dodger attempt a rescue. Roscoe and DeSoto fall off the car in the struggle and land on the subway's third rail, which electrocutes them. Tito takes control of Fagin's scooter as Fagin manages to retrieve Jenny, and Tito drives it up the side of the Brooklyn Bridge as Sykes' car drives straight into the path of an oncoming train, killing him and throwing him and his car into the Hudson River. Dodger and Oliver manage to survive the collision and are reunited with Jenny and the others. Later, she celebrates her birthday with the animals, Fagin, and Winston. That same day, Winston receives a phone call from her parents in Rome saying that they will be back tomorrow. Oliver opts to stay with her but he promises to remain in contact with Dodger and the gang.
But then in a epilogue, on a rainy day a person goes fishing at the New York docks, when all the sudden his fishing rod gets dragged in the water, and soon he begins running for his life when some spikes stick out of the water and destroy the dock, and an eye opens to some homeless people. Thus, leading up the events to Brian and the Eeveelution Family's Adventures of Godzilla.
- The Griffin Family, Vinny Griffin, Glenn Quagmire, Cleveland Brown, Joe Swanson, Little Bear, Duck, Cat, Owl, Hen, Emily, Lucy, Mitzi, No Feet, Tutu, Doug Funnie, Skeeter Valentine, Roger Smith, Bender Bending Rodríguez, Minerva Mink, Sheeta, Pazu, The Crystal Prep Girls, Wubbzy, Widget, Walden, Daizy, The Young Six (Silverstream, Smolder, Ocellus, Sandbar, Gallus, and Yona), Blythe Baxter, Zoe Trent, Pepper Clark, Penny Ling, Vinnie Terrio, Sunil Nevla, Minka Mark, Russell Ferguson, Mitzi, Dudley Puppy, and Kitty Katswell guest star in this film.
- It is revealed that Georgette and Zoe Trent are old friends.
- Opening/Once Upon a Time in New York City
- Oliver Meet Dodger, and our heroes/"Why Should I Worry"
- At the dock/Sykes, Roscoe, and DeSoto arrive
- Bedtime story
- The next morning/Streets of Gold
- Sneaking into the limo
- At the Foxworth's house/"Perfect Isn't Easy"
- Georgette meets Oliver/the rescue plan
- "Good Company"
- Sneaking into the house/rescuing Oliver
- Sad moments/Fagin gets an idea
- Where's Oliver?/the letter/at Sykes' building
- Jenny meets Fagin/Jenny gets kidnapped!
- Rescuing Jenny
- Pursuit Through the Subway
- Jenny's birthday/happy ending
- Epilogue: A new threat