Once a feared supervillain trio, the Ministry of Pain terrorized Townsville for many years but were always thwarted by Captain Righteous and his sidekick Lefty. In the present they are now of advanced age and no longer physically fit to continue their lives of crime, and for a time lived in quiet retirement where they could no longer do anyone harm.
They are first seen in "Fallen Arches" when Mastermind gets his old villain team back together. Angry and bitter over the love and praise the Powerpuff Girls get for stopping evildoers in the city, Mastermind decides to resume his life of crime, counting on his old age and his infamous past to keep the Girls from interfering. Sure enough, during a bank robbery, the Girls confront the trio, but Blossom refuses to let Buttercup or Bubbles fight them as she says that they must respect their elders. The Ministry is allowed to escape, and the Girls are scorned by the public for failing to act.
After talking to the Mayor who refuses to believe the Girls are capable of taking on the three extremely frail men, the Girls learn that Captain Righteous and Lefty were the Ministry's greatest adversaries and Blossom elects to recruit the two men to fight the Ministry in their stead. The two men agree, though the Captain is unaware that Lefty, who he's grown to resent, will be fighting alongside him. At another bank robbery, the Ministry of Pain makes their getaway until the Captain and Lefty arrive, only for them to get in an argument over who deserves credit for the villains' capture. Mastermind shoves Lefty aside, causing him to break his hip. Distressed at his old friend's injury, Captain Righteous launches himself at the Ministry of Pain, badly injuring all three men and himself in the process.
The Ministry of Pain and the two superheroes are immediately rushed to the hospital, and on the news it's revealed that they're all expected to be okay. However the public and the media criticize the Girls as it was their hesitation to fight that led to the unfortunate incident. Blossom in particular is scorned by both Bubbles and Buttercup for having caused the five men to get hurt, and she slinks away in shame after watching the news.
The Ministry of Pain was never seen again afterwards, presumably having returned to their retirement as the three men were likely no longer fit to resume their evil ways again after their injury.
- Mastermind: The leader of the group, he is an aged old man with a large, bald head. A scar running down one cheek, and he wears a monocle with a permanent, very sour expression. His room is red and black and he wears a black outfit with a skull on the front.
- Counterpart: Large fat one. He was muscular during his youth and also wears a belt with a dropped skull attached.
- Cohort: The shortest of the three, who also wears glasses and the same skull belt as his teammates'.