Fifty years ago, before the creation of Naraku, Mistress Centipede was one of the most powerful yōkai in that era. She defeated various other yōkai and obtained the Shikon no Tama until she was slain by a group of Yōkai Taijiya. It was removed by Sango's grandfather the day after she was killed but she was still able to regenerate thanks to the jewel being near her corpse, but ultimately she was driven away by the demon slayers. She later attempted to take the young Kaede hostage and use her as a bargaining tool to obtain the Shikon no Tama from Kikyō. The demon's plan was cut short when she was killed by Inuyasha for the first time.
Kikyō acknowledged that as long as Mistress Centipede's body was near the jewel she would resurrect to no end. Kikyō had her followers collect all remains of this fearsome demon and throw it down the Bone-Eater's Well, so that the power of the Shikon no Tama would not be able to revive her again.
In the present era she was able to resurrect herself and attempted to take the Shikon no Tama from Kagome Higurashi's body, dragging Kagome from the modern world to the Feudal Era in the process. In self-defense, Kagome was able to use spiritual power to destroy one of Mistress Centipede's arm which forced her to retreat into the time hole. She resurfaced later that night to take the jewel again and followed Kagome when she ran toward the Goshinboku which Inuyasha was sealed to. The demoness attempted a second time to take the jewel but Kagome was again able to blast off the rest of her arms. Enraged, she bites Kagome, tearing the Shikon no Tama out of her body. The demon then binds Kagome along with Inuyasha to the tree while she swallowed the Shikon no Tama. With the power of the Shikon no Tama, Mistress reattached her five arms and transformed into much more formidable demon. Despite being powered-up by the jewel, she was easily defeated by Inuyasha once he was freed from the Goshinboku. The Shikon no Tama inside her flesh was removed and her body turned into bones, finally putting an end to the fearsome yōkai's life.
- Tornado Twister: She rapidly spins her body in a tornado-like motion, which turns it into a weapon. Because she is spinning around so rapidly, she can do a great deal of damage to humans.
- Enhanced speed & agility: Despite her large size Mistress Centipede was rather agile and quick, so she was capable of catching up with most other demons.
- Regeneration: As long as there is the Shikon no Tama nearby, Mistress Centipede cannot be truly killed.
- Time Travel: Mistress Centipede is unique that, like Inuyasha, she can travel between the Feudal Era and the present.