The Powerpuff Girls face their greatest challenge in this 10th anniversary special episode. There exists a Key to the World, which is handed from city to city on an annual basis. Whoever possesses the key rules over the entire world. When the key is delivered to Townsville, every villain in Townsville attempts to retrieve it. When the girls procure it for themselves, they quickly get sucked into a power struggle, fighting the villains and themselves over who gets to rule the world.
Cathy Cavadini
as Blossom (voice) (as Catherine Cavadini)
Tara Strong
as Bubbles / Alarm System (voice)
E. G. Daily
as Buttercup (voice) (as E.G. Daily)
Tom Kenny
as Narrator / Mayor / Dove (voice)
Tom Kane
as Professor / Him / Talking Dog (voice)
Roger L. Jackson
as Mojo Jojo (voice)
Jennifer Martin
as Ms. Bellum (voice)
Kevin Michael Richardson
as Fish Balloon (voice)
Jeff Bennett
as Ace / Prisoner / Concerned Citizen (voice)
Jim Cummings
as Fuzzy Lumpkins (voice)
Jennifer Hale
as Princess (voice)