Buttercup moved, along with her sisters Bubbles and Blossom, to Megaville from their former home in "The City of Townsville," and attended the Megaville Elementary School. On the first day of school, Buttercup had an altercation with Dexter, but the fight was broken up by the school's gym teacher Jack. Later on, Buttercup was inside with Blossom and Dexter, when Courage approached them and said that Bubbles was being attacked by the "Dread Dragon". A monster created by Mojo Jojo, and sent to destroy the Powerpuff Girls. The three of them fought it and managed to rescue Bubbles, but Buttercup was captured in it's mouth towards the end of the battle. It was at that point that Jack arrived at the battle and slayed the monster, saving Buttercup from it.
After this incident, Buttercup wasn't seen for a while, until the fight between Dexter and Mandark. Buttercup helped Coop and Megas in their fight with Samantha, who, at the time, was about to kill Coop, so Buttercup surprised Samantha with a "sucker punch." Samantha was a being whom was brought back by one of the members of the "Darkstar Council". When Mandark summoned a giant Cluster robot that captured Dexter, Buttercup smashed it, freeing Dexter and then escaping along with the girls and Dexter on Megas.
Later, after helping Dexter and her sisters beat the Globmonster, Buttercup was asked by Bubbles if she wanted to participate the try-outs for Megaville Dance Troupe. Buttercup refused the offer as she wanted to attend Kendo class. In the Kendo class, Jack described the noble art of Kendo. This felt on deaf ears however with Buttercup, whose love for fighting led her to easily and handily beat-down everyone she faced, before being stopped by Jack. As a penalty, the Professor was forced to go and speak with Jack about her impulsive behavior. It was decided that she wasn't going to be grounded but instead, Courage would have to be with her the at all times and take notes of her actions, in order to insure she would behave properly. The Professor also thought it would be better if she did other activities. He first let her try out a science course, but that didn't work out, with Buttercup's impatient personality. So instead, they tried a cooking course, which, oddly, seemed to fit better with Buttercup, and so it became a success.
At a later point, Buttercup was going to attend the science fair, in order to make snacks, along with Jack, and sell them to the students and visitors. While they were about to watch a special dance performance, GIR suddenly intruded on the event and Jenny went to try and get rid of him, but GIR, instead, placed a machine on her head, which turned Jenny into a portal between the Cluster Zone and Megaville.
When this occurred, Buttercup encountered Samantha again and battled against her, along with Jack. Despite his efforts, Samantha defeated Jack and stole his trademark katana, but Buttercup would continue the fight with her in an effort to get it back. Samantha then attempted to make her way to Bell, but Blossom and Buttercup followed her. There, Buttercup fought Samantha again, but she eventually retreated from the battle, and instead, went after Blossom and Bell, while Buttercup was occupied in a fight against another, giant Cluster. After defeating the Cluster, Buttercup resumed her pursuit and followed Samantha, Blossom, and Bell.
She caught up with Samantha who was about to attack Blossom. But luckily Buttercup grabbed Samantha and tossed her away, allowing Blossom to proceed. Buttercup continued with a barrage of attacks on Samantha, mocking her in the process, making Samantha deadly furious. Buttercup's attacks exposed more of her robotic body, and Buttercup got the upper hand. However Samantha launched a rocket fist at Buttercup's head, which was followed by a punch of Buttercup against Sam's jaw. Samantha then threw chains towards Buttercup which tied around her legs, followed by Sam grabbing her limbs with her chain arms. Sam charged up a laser, but got interrupted by the energy balls that were reflected by Blossom down below. One of the energy balls went right through Buttercup and Samantha, destroying the hand, and blaster, of Samantha, as well as the chain that held Buttercup's limbs. Buttercup noted that it would sting, following by a backflip which caused the balls on the chains, around her legs, to jam into Sam's face. She quickly untied the chains, while questioning who used chains in a battle, and headed down below to the fight of Blossom and Bell.
She came right in time to block the incoming attack of Bell on Blossom, by taking all of the damage to the left side of her head, making it bleed. Buttercup quickly sent her flying with a punch. Buttercup helped Blossom got up and reattached her bow on her head, although not as she always wears it. Buttercup proceeded by ripping off a part of her shorts to conceal the burn wounds of her sister, while they talked about each others wounds. Blossom in turn ripped off a piece of her shirt to treat the bleeding wound on Buttercup's forehead. Samantha then also joined in again, so Blossom and Buttercup decided to take a different approach.
While Blossom fought Samantha, Buttercup headed over to Bell. They clashed by bashing both their hands into each other. Buttercup quickly reacted and threw Bell into the air, while still holding her. GIR then wanted to throw a bomb from a slingshot at Buttercup, but she destroyed it with her laser. Bell commanded Buttercup to put her down. So, Buttercup grabbed Bell and performed a final atomic buster on Bell. GIR fired smoke bombs, disabling Buttercup from doing anything. Samantha saw the opportunity and wanted to attack Buttercup, but Blossom quickly followed her into the smoke cloud. It ended up with Samantha grabbing Blossom with her mechanical tentacles, and holding the katana against her throat. She mocked Buttercup by saying that she was going to kill Blossom. She then slitted the throat of Blossom but nothing happened because the katana only can hurt evil. As Samantha was surprised, Buttercup bashed into her to free Blossom, and rapidly beated her. Blossom hugged and thanks Buttercup, but that moment was quickly interrupted when Blossom didn't know what to do anymore. With Samantha planning on using GIR as a conduit to activate the bomb after all, an act that Bell would never allow. As Bell was ready to throw Jack's katana to stop Samantha, Blossom had to make a decision whether to keep hugging Buttercup or to push her away to let the katana go between them. She chose the latter which results in the katana piercing through Samantha. This caused her to step back, and fall in the electricity and completed the circuit of the machine again and triggered the bomb. Blossom realized she had made the wrong choice and realized she killed Samantha and activated the bomb. She fell on her knees in despair, while Bell and GIR escaped, though Buttercup wanted to go after them. As Blossom and Buttercup were leaving, they were stopped by Dee Dee, holding the katana, who asked them to follow her.
While Dee Dee flying them into the stage. Blossom asked her question after question but Dee Dee stated that she wasn't supposed not to talk about her nature.As they flow through, Buttercup commented on the death of Kuwagus. And finally they reach in the stage where Dee Dee need to go. Both Blossom and Buttercup were shocked too see the Rowdyruff Boys in front of them. As Blossom started to argue with Brick, Buttercup said that they weren't ready for another fight now, but Blossom revealed that she was just winning time. As Blossom had expected, Brick started to monologue but before the brothers could do any damage, they were stopped by I. M. Weasel. As the professor had come along with Weasel, he quickly hugged Blossom and Buttercup. After he released her, she helped Jack and returned his sword to him. Meanwhile, Boomer got the crazy idea to kiss Bubbles, to see if she would explode, much to surprise of anyone. This caused great distress in Bubbles, before Blossom explained again that she isn't at risk because, physically speaking, she is stable, only she did start to question her mental stability. After nothing happened, Boomer started kissing the other women in the room, much to the embarrasment of his "victims". Buttercup, already angry about the fact that he kissed her sister without her permission, was infuriated when he kissed her. Blossom tried to calm her down as Boomer continued his kissing spree by kissing Agent Honeydew. Honeydew is slightly annoyed by this, but to Buttercup's surprise neither she or Jack lash out at him, instead trying to help understand the world better. At that moment, Monkey returned to Earth and was hugged by Honeydew. Jack stated that he was happy to see them reunited, for which he was thanked by Honeydew, who placed her hand on his shoulder, much to the disapproval of both Buttercup and Monkey.