The series follows Blythe Baxter, a young girl living with her air pilot father, Roger. Forced to move out from her suburban hometown following her father's promotion, she moves into an apartment located in a crowded city. Their complex is located above the eponymous Littlest Pet Shop -- a pet store that also serves as a day camp for numerous pets -- where Blythe works as a fashion designer. Her adventure begins when she discovers that she alone can miraculously understand and talk to the pets that regularly stay at the shop, in addition to most other animals on the planet. As she and the pets spend time together, they find the pet shop jeopardized by a larger pet store managed by Fisher Biskit and his snooty twin daughters, Whittany and Brittany Biskit. To avoid being dispersed, the pets convince Blythe to remain an employee.
The pets who reside in the day camp of the store are Pepper, a wisecracking skunk passionate about comedy; Minka, a bouncy spider monkey with a flair for painting and visual arts; Penny Ling, a sensitive giant panda interested in rhythmic gymnastics; Russell, a hedgehog who is often the self-appointed leader of his animal bunkmates; Sunil, a mongoose and magician hopeful; Vinnie, a clumsy gecko obsessed with dancing; and Zoe, a diva-like dog with a talent for singing. Other human characters include Mrs. Twombly, owner of the shop and Blythe's boss, and Youngmee Song, Sue Patterson, and Jasper Jones, Blythe's schoolmates.