After moving into an apartment, Blythe Baxter gains the ability to communicate with animals after falling in a dumbwaiter. There, she meets a group of pets who reside in a day camp area of a pet shop, who enlist her help when the store is on the verge of running out of business.

Blythe stumbles to fix a botched haircut on Zoe, while the other pets urge Minka to purse the life of an art superstar, and get out of hand when they overestimate her artistic endurance.

Blythe uses the pets as diversions in order to rescue Zoe's sister from inside Largest Ever Pet Shop, an expansive pet store retail chain owned by the Biskit twins' father, Fisher Biskit.

Blythe earns the gratitude of the Biskit twins after defending them against a bully during gym, but ends up being forced from talking her other friends. Meanwhile, Pepper is inspired to use insult comedy as part of her stand-up comedy schtick, but takes it too far on Penny while being unaware of her sensitive feelings.

Blythe rejects the notion of her dad going on a date to a charity ball, while Penny Ling struggles to voice her disapproval of an outfit Blythe designs for her to wear at the ball along with the rest of the pets.

Suspecting that he has become too serious for his own good, Russell loosens up by creating an alter ego, dubbed "Fun Russell". Meanwhile, Blythe finds her friend Sue mimicking every aspect of her personality unsettling.

Blythe stumbles upon some keys belonging to her crush, Josh Sharp, and goes searching for him using Sunil's precognition. When he assumes she has gotten lost due to his own lack of faith in his psychic abilities, he enlists the help of his friends, along with larger-than-life parrot Esteban Banderas.

While on her way to meet with her friends at a flash mob, Blythe gets trapped in the dumbwaiter along with Zoe, Pepper and Minka. While Penny Ling tries to attract the attention of the boys to get them out from the dumbwaiter, Zoe and Pepper start to fight, and within their compact space, Minka's claustrophobia is triggered.

Blythe attempts to be the peacekeeper between Zoe and her old rival Madame Pom when arrives at day camp, all the while Penny Ling and Vinnie nearly destroy the shop while practicing for their new group dance routine. Likewise, Mrs. Twombly goes on a rampage in search of her favorite cleaning spray.

The pets suspect a Siamese cat visiting the day camp is preying on Mrs. Twombly. Meanwhile, Blythe encourages the Biskit twins to join their mathlete team after she overhears them using narratives of their daily life to solve complex math equations.

Vinnie gets to tour the set of his favorite dance competition show, Shake a Leg. When his dance performance in front of the show's judges gets harshly rejected, he tearfully abandons Blythe into the streets, where he befriends an ensemble of street-dancing lizards. Meanwhile, the pets stumble around trying to find a decent spot for their remote control.

Sunil is mistaken for Shahrukh, a famous movie mongoose hailing from India. The pets bend over backwards to appease him, but quickly lose their patience at his pampered behavior during his stay at the day camp.

Zoe, temporarily bandaged due to an embarrassing pimple on her nose, asks Penny Ling to pass along her romantic feelings to her crush, Digby, during his stay at the day camp. Meanwhile, Russell hides in Blythe's backpack, wanting to pursue an education, but gets lost within the corridors of her high school.

Youngmee's Aunt Christie opens a confectionery store adjacent to Littlest Pet Shop, and the pets meet pet Buttercream Sunday, a hyperactive rabbit, who invites them to overindulge themselves on the sugar-filled treats located in Christie's pantry.

Surrounded by guilt, the pets try to prove Blythe's innocence after she is accused of sending Aunt Cristie's truck careening down the street while meeting Buttercream's alley cat friend, Sugar Sprinkles.

Minka tries to befriend an antisocial tortoise named Olive Shellstein, who is dropped off at the day camp, but stumbles to get her out of her shell before she has to leave. Meanwhile, Roger surprises Blythe at her high school, wishing to spend the day together.

Blythe enlists the pets to retrieve her new favorite necklace that fell inside a vat of batter used for filling a huge cupcake order with Youngmee. This proves difficult for them, when they discover the order was placed by Fisher Bisket for his twin daughter's "quarter-birthday" party.

Vinnie accidentally falls into a dumpster while trying to catch a fly and is transported to the dump, where he encounters a rat that helps him get back to the pet store. Blythe contracts the common cold and can no longer understand the pets, so the pets try to cure her.

Russell, Zoe, and Vinnie, along with Buttercream, try to retrieve a recipe stolen from Blythe by the Biskits, who plan to use it for a baking competition hosted at Blythe's school. All the while, Vinnie has a vision of cakes occupying the world.

Zoe begs for Blythe to enter her in a reality television series based on a beauty pageant for dogs. What starts off as enjoyable starts to consume Blythe, who becomes driven by winning the pageant, much to the dejection of Zoe.

Blythe discovers Mrs. Twombly's past as the inventor of a unique martial art. Meanwhile, Pepper's comedy idol, Old Bananas, comes to visit the day camp, but finds herself struggling to amuse him with her jokes, in order to earn his signature thumbs up of approval.

Sunil and Vinnie hear howling noises coming from inside the pet shop, and suspect that their friends have turned into werewolves. When Mrs. Twombly finds she has been outbid at an online auction for a highly coveted doorknob by her rival, Fisher Biskit, she takes Blythe and herself for a visit to his mansion to find its whereabouts.

Vinnie's tail falls off in an act of autotomy, and after a series of trials to find an adequate replacement for it, he is shocked to find that he becomes better at dancing without one. Meanwhile, Zoe and Pepper become rivals over the theme for a party meant for Penny Ling.

While searching for Mrs. Twombly's missing glasses, Blythe comes across Shivers, a fast-talking squirrel with a hoarding problem. When Blythe and the pets realize Shivers is at fault for items missing from Littlest Pet Shop, they try to help him face his issue.

When Blythe gets accepted into the junior program at a fashion school, she, along with her family and friends from school and at Littlest Pet Shop, have to bode with the anxiety of her leaving.