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.

• Cartoon Network Studios
• Cathy Cavadini
• Tara Strong
• Elizabeth Daily
• Tom Kenny
• Tom Kane
• Roger L. Jackson
• Jennifer Martin
• Kevin Michael Richardson