A late 20th-century New York City pizza delivery boy, Philip J. Fry, after being unwittingly cryogenically frozen for one thousand years, finds employment at Planet Express, an interplanetary delivery company in the 31st century.

Chip and Dale, two chipmunks with a nose for trouble, start a detective agency, Rescue Rangers, along with their new friends Gadget, Monterey Jack, and Zipper. The pint-sized detectives deal with crimes that are often "too small" for the police to handle, usually with other animals as their clients. The gang frequently finds itself going up against two particular arch villains: Mafia-style tabby cat Fat Cat and mad scientist Norton Nimnul (both voiced by Jim Cummings).