The show featured pups Cooler (the leader), Howler (the inventor), Bright Eyes (the youngster), Whopper (the comic relief), and Nose Marie (the beautiful but conceited Southern Belle). The five pooches operated a computer-controlled underground facility that matched up needy dogs with loving families.

The gang's headquarters was located on the lawn of the rich Millicent Trueblood (voiced by TV legend June Lockhart). Blessed with “puppy power,” Millicent was able to talk to the dogs and keep abreast of their goings on. Unfortunately, Millicent died and the mansion was inherited by her evil grandniece Katrina Stoneheart.

Katrina’s plans to tear down the pound were foiled when it was discovered that the pound and all the surrounding land actually belonged to the Katrina’s soft-hearted ward, Holly, who coincidentally also possessed the “puppy power.” Holly became the new human protector of the Pound Puppies, defending them against attacks from Katrina, her daughter Brattina, and their bad kitty Cat-Gut.

In the show's second season, the title was changed to The All-New Pound Puppies.

Pound Puppies may have begun simply as a way to sell toys, but the sharp writing of the series set it apart from its like-themed competition, The Care Bears or My Little Pony. Hip spoofs of pop culture and music videos gave the show enough substance to entertain kids of all ages. The cartoon also featured a segment called “Pet Care Corner” which gave advice for kids with pets.