A young, lonely Shaggy Rogers befriends and adopts a stray talking dog, whom he names Scooby-Doo. Their bond is instant and inseparable. Soon, they team up with young detectives Fred, Velma, and Daphne to form Mystery Inc., solving various local crimes and mysteries. After years of amateur sleuthing, the gang faces the prospect of going their separate ways as they reach adulthood. However, before they can disband, they stumble upon their most challenging mystery yet.

During the grand opening of a popular food chain's latest location, Shaggy and Scooby-Doo are attacked by robotic minions and rescued by Blue Falcon and his robot dog Dynomutt. They learn that their assailant was Dick Dastardly, a villain in search of three skulls that will unlock the gates to the underworld. The gang reluctantly teams up with the superheroes to stop Dastardly, while also trying to understand the true significance of their friendship and each member's role within the group.