This movie changes the primary focus of the series from Buddy, an adult golden retriever, to his puppies. It also radically alters the character of the series by making all of the animals speak.
Through a voiceover, Sniffer (voiced by Don Knotts) introduces the five Air Buddies, describes their personalities and recaps how the puppies' father, Air Bud, made the town of Fernfeild famous through his love of sport. When their families leave home for a basketball game, the puppies get into trouble with their sitter, Mrs Niggles. This prompts their owners to finally put the puppies up for adoption.
Meanwhile, Selkirk Tander (Holmes Osborne) tries to impress Mr. Livingston's (Steve Makaj) son, Bartleby Livingston by showing him a female tiger for his birthday, but Bartleby wanted an animal he can play with. He wants Air Bud (Buddy) because Buddy can play sports. Mr. Livingston offers $500,000 if Selkirk can get Buddy. Selkirk then sends his nephew Grim and assistant Denning to capture Buddy.
At school, Noah and Henry collect every boy and girl's profile sheets and photos, and after looking at girls and boys who would make good owners, the family decides to call their new owners the next day. Grim and Denning arrive at Buddy's home, only to see Buddy and Molly at the same time, thinking there are two air buds or they are mates. The next morning, the pups decide to run away. Grim and Denning follow them, and manage to catch Budderball by luring him with a doughnut. The other Buddies go and find Budderball but they are captured as well and used as bait to catch Buddy and Molly. Buddy manages to free the Buddies but Denning traps him with a net. Molly attempts to save Buddy but is captured too. Denning and Grim put Buddy and Molly in the truck, while the buddies chase after them.
In wine country, Selkirk is pleased that Denning and Grim captured both Buddy and Molly so he can have them breed puppies and sell them for money. When Grim explain that Buddy and Molly already had puppies and Denning let them get away, Selkirk tells them to lock the dogs in the wine cellar and go and capture the puppies and threatens that if they don't catch the puppies, they will be fed to the tiger. Selkirk also replaces Grim as the leader of the mission to capture the Buddies. Grim and Denning go back to Buddy's home to capture the Buddies but no luck. The Buddies have sniffed their way to the outside cinema, where Grim and Denning are watching 101 Dalmatians. The Buddies find their way to the projection room and walk right in front of the projector, their shadows attracting Denning and Grim's attention.
Grim and Denning catch up to the Buddies, chasing them to a farm. The Buddies meet Billy the Goat and Belinda the Pig, who help the Buddies escape from Grim and Denning. The Buddies lure Grim and Denning into a stable and escape through a small hole as Billy locks Grim and Denning in. The Buddies go through the forest then meet the Wolf who leads them to wine country. A skunk's spray enables Sniffer to smell again, so he calls Noah and Henry and they go off to find the Buddies. Buddy and Molly manage to escape to find the Buddies. Budderball falls into a hole, which Buddy and Molly dug, forcing the Buddies to help. Noah and Henry are led by Sniffer through the same farm that the Buddies went through. Noah and Henry are ecstatic and overjoyed at finding Grim and Denning being held prisoners by Billy the goat, and immediately depart to report them and turn them in to the authorities over Grim and Denning's protests. Bartleby and his father come to collect the dogs but instead finds the Buddies. Bartleby and his father then put the Buddies in a limousine, when Noah, Henry, Buddy and Molly come to rescue the Buddies. Budderball falls into one of the wine containers and gets drunk. Bartleby catches Budderball but is caught by Sniffer.
Noah, Henry, and the dogs release barrels towards Selkirk and Mr. Livingston; the barrels break the wine container. Selkirk and Mr. Livingston fall in, as the container cracks open. Washing out of the container, Sheriff Bob arrives to arrest Selkirk, Denning, and Grim. The Buddies apologize to Buddy and Molly; they understand and say they're ready for their new owners. Budderball decides to stay with Bartleby because he needs a friend. The puppies are introduced to their new families and end up enjoying their new lives.The film ends with Buddy, Molly, Buddha, Budderball, Rosebud, B-Dawg, Mudbud, Sniffer and The Wolf howling to show how they are still family, despite their separation from each other.Slade Pearce - Noah Framm
Holmes Osborne - Selkirk Tander, the villain of the movie.
Trevor Wright - Grim, Selkirk's foolish nephew.
Paul Rae - Denning
Christian Pikes - Henry
Patrick Cranshaw - Sheriff Bob
Tyler Guerrero - Bartleby Livingston
Steven Makaj - Mr. Miles Livingstone
Richard Karn - Patrick Framm
Cynthia Stevenson - Jackie Framm
Jane Carr - Mrs. Niggles
Scout and Parker - Air Bud (because of the demanding schedule, the role was played by more than one dog)
Abigail Breslin - Rosebud - the lone girl and only sister of the Buddies. She always wears a pink bow in her fur (usually her head) to separate herself from her brothers. She is protective of her brothers and her favorite color is pink.
Dominic Scott Kay - Buddha - the peaceful Buddhist of the Buddies. He loves to meditate and wears a Buddhist collar made of beads. He is named after a virtuous person, Gautama Buddha.
Josh Flitter - Budderball - The chubbiest of the Buddies. He enjoys food and wears black ink on his face to look like a football player. In addition to this he also sports a red football shirt. When his paw is pulled, he releases unbearable gas from his bottom, an allusion to Pull my finger.
Spencer Fox - Mudbud - The dirt-loving dude of the Buddies. He wears a blue handkerchief around his neck.
Skyler Gisondo - B-Dawg - The hip-hoppin' pup of the Buddies. He loves rap music and wears a platinum chain with a 'B' as a pendant around his neck to look cool and hip.
Tom Everett Scott - Buddy - The father of the Buddies. He's still as fun-loving and athletic as he was before the Buddies were born. He belongs to Noah.
Molly Shannon - Molly - The mother of the Buddies. She loves her children and Buddy very much and will do anything to protect them. She belongs to Henry.
Michael Clarke Duncan - The Wolf - The Wolf is a friendly inhabitant of the forest who helps the Buddies get to wine country.
Don Knotts - Sniffer - An old Bloodhound who lost his sense of smell years ago. He later regains it after getting sprayed by a skunk. He is one of the characters in the movie who help the Buddies find their parents.
Wallace Shawn - Billy - a goat who the Buddies meet on the farm. He helps keep the Buddies out of Grim and Denning's clutches.
Debra Jo Rupp - Belinda - a kind sow who the Buddies meet on the farm and speaks Pig Latin.
B-Dawg is the pup who can play basketball, while Budderball plays football, Rosebud plays soccer, Buddha plays baseball, and Mudbud plays volleyball. All the animals can speak in this film. This was the first time speaking animals have appeared in the Air Bud series.
Patrick Cranshaw died on December 28, 2005, but he had already finished filming all of his scenes for the movie. Don Knotts died on February 24, 2006, but he finished all his voice work on this, his final film. The movie is dedicated to them both.
The next movie of the series is Snow Buddies.