Itchy is unable to properly beg for food, unlike Charlie, who masters it quite often. Under Charlie's guidance, Itchy begs a spoiled rich girl for ice cream, who, in return, takes Itchy as a new pet. Meanwhile, Carface and Killer have picked the same house as their next target in a string of burglaries.

It's David's 10th birthday and he's received a voice recorder. However, it gets him study hall from the vice principal, so Charlie and Itchy bust him out for a day of fun but must watch the clock to get their human friend back in time.

Carface and Killer steal Itchy's Heavenly Collar, so Charlie, Itchy, and Sasha plan to get it back. When the plan involves Sasha flirting with Carface, Charlie's jealousy gets the better of him.

Charlie auditions to be the new spokes-dog for Gulpo Dog Food, but the company picks Itchy instead. Now Itchy's famous and Charlie's left sulking in the Flea Bite Café, leaving everyone wondering, 'Will success spoil Itchy Itchiford?'

Annabelle assigns the duo on a mission to help a boy named Leon join his Little League team. What Charlie doesn't know is that this is Itchy's twentieth mission, and if successful, he will be reallowed entry to Heaven. With the separation between him and his best friend at stake, Charlie struggles with moral dilemma: to deliberately tank the mission or help out and let Itchy go back to Heaven.

Sasha wants a 'perfect dog' and Charlie takes advantage of being hit by a car to smother her in love and kindness, until she goes mad.

Charlie and Itchy are assigned to return a cat named Dilly to her owner, but when Dilly gets taken in by a dog-hating cat lady, the duo must use a Miracle Dog Tag to become cats to rescue her.

Charlie volunteers to go get notes that David's crush Alex left in her mom's car, but Sasha must go with Charlie instead. Charlie, however, doesn't see women as good partners for this type of thing. Sasha decides to show Charlie what women can do.

Itchy is frightened by a wilderness movie, but Charlie tells Itchy that every dog has wolf blood in them, even Itchy. And so Charlie decides that they are going on a trip into the wild, so Itchy can live up to his heritage. They encounter a lost girl scout named Charlotte, and help her find her troop.

Charlie decides to try Kibbleland's new game, but he becomes selfish to not only think of himself and nobody else, not even Sasha. This becomes serious when Belladonna tricks Sasha into playing the game as a big tornado approaches and sucks her into the world of Kibbleland. The duo must find a way to rescue her before she's trapped forever.

Assigned to guard a crystal, Charlie and Itchy continue goofing off, but Charlie becomes convinced he's seen a UFO and Itchy doesn't believe him. The 'aliens', actually Carface and Killer, break into Charlie and Itchy's home and steal the crystal, prompting Charlie to get it back.

Charlie has been lying a bit too much lately, so Anabelle makes his nose grow every time he tells a lie. Charlie must start telling the truth or face the consequences.

The next mission takes Charlie and Itchy to the sewers to help a colony of mice. Toxic smelling paint and other junk washed down the drains, taking away their freedom of living without worries. They join forces with Moxie, a mother mouse in the colony, to crack the case, and follow the drain to Carface and Killer's curio shop, where the villainous duo trying to transform new looking toy trains to look like antiques to sell for big money.

Circus animals are being mistreated, and Charlie and Itchy are on the case. They learn that an elephant named Nelly is abused, and it's their job to videotape it and send it to Animal Control.

Charlie and Itchy are sent to a military base and show a kid how to have fun, but Anabelle also sent them there so Charlie would learn some respect for authority figures.

Charlie and Itchy are assigned on a mission to watch an absent-minded scientist. Armed with a Miracle Dog Tag, supposed to be used for emergencies only, Charlie persuades Itchy to let him have it, turning himself into a human.

Itchy and Charlie write a report for David on the history of all dogs and how they helped society.

Charlie and Itchy take a stroll on the upper-class neighborhood and meet a rich show dog named Thor, who looks exactly like Charlie. Charlie wants to know what it is like to be pampered, and Thor wants to know what it is like to be a free-spirited street dog, so the two switch places. When Thor's agility contest comes up, and Charlie's expected to do a dangerous move, Charlie soon realizes that switching places between each other is more difficult than at first thought.

Charlie dreams a bad future for himself. When it takes him to a future where dogs live under the oppressive rule of the canine-hating 'Deliverer', he decides to change his ways before it's too late.

Carface gets his hands on a dangerous substance able to turn dogs into monsters. He and Killer taint Charlie's dog food, and Charlie turns into a monster. Carface and Killer plan to use Charlie to steal for them, and then turn Charlie in. Itchy learns about this situation and goes to rescue his best friend.

Charlie is assigned to train three potential angels, but when he fails, and he needs their help, they mess up, getting Charlie in deeper trouble.

Itchy tells the story of the amazing Double Dog Dare and how he saved the world.

Itchy accompanies Bess to her dog school reunion, with Itchy pretending to be of pedigree. Afghan Hound Tiffany humiliates Bess, sparking Charlie to prank her, but it only makes everything worse. After Tiffany puts fleas on Itchy, the beam she's standing on collapses. With the other dogs unwilling to help, it's Itchy to the rescue.

Charlie recounts how he met Itchy, and how he'd been a bad dog to a pair of puppies arguing over a bag of dog food.

Charlie becomes obsessed with being recorded doing a heroic act. That is, until Itchy almost drowns, but the reporters catch him saving Itchy, and the two get to go to an exclusive hotel suite.