Mindwipe was part of the team of Decepticons who participated in an operation to seize the key to the Plasma Energy Chamber from the Autobots. During the battle, the key was briefly used to open the Plasma Energy Chamber, causing it to throw both the key and several Autobots across the galaxy to the planet Nebulos. Mindwipe and several other Decepticons were then sent to Nebulos to retrieve the key.
In the initial scuffle on the planet, the Decepticons managed to capture several of the Autobots, but the Autobots managed to rescue their allies by becoming binary bonded to a group of Nebulan rebels, turning them into powerful "Headmasters". After being defeated by the Autobot Headmasters, Mindwipe and the Decepticons were forced to flee into the wilderness of Nebulos. They soon encountered Nebulos' corrupt ruling council, the Hive, and were brought before them. The Decepticons made a deal with the Hive's leader Lord Zarak to become binary-bonded with the members of the Hive to combat the Autobot Headmasters. Mindwipe's head was thus re-engineered to become an exo-suit for the Hive scientist Vorath. Though Vorath was reluctant to be paired with a "mangy night-scavenger", Mindwipe simply hypnotized Vorath and forced him to combine with him.
The Decepticon Headmasters then launched an attack the Autobots. Using his extra-sensory powers, Mindwipe discovered that the Autobot Brainstorm was the one holding onto the Plasma Energy Chamber key. After having Vorath shoot the Autobot, the Decepticons took the key from his fallen body and all returned to Cybertron with their new Hive allies to help Galvatron fight off the Autobots on the planet.
In the battle for Cybertron, Mindwipe fought and defeated Ultra Magnus with assistance from Weirdwolf and Apeface. Galvatron then used the key to open the chamber, planning to use it to destroy Cybertron and Earth. After Galvatron's plan was foiled, Mindwipe and the Decepticons escaped aboard Scorponok, only for a plasma energy shot to knock them into the depths of space.
Four million years ago, Mindwipe was among a group of Cybertronians who left Cybertron under the leadership of Fortress to escape the eternal war that had consumed the planet. After crash landing on the planet Master, the Cybertronians made several technological quantum leaps to survive in the planet's inhospitable atmosphere and rapidly-changing environments, including the creation of larger, lifeless Transformer bodies called transtectors that would allow them to become "Headmasters". However, Mindwipe and several others ended up rebelling against Fortress and siding with a traitor named Scorponok.
The traitorous Headmasters later pledged their allegiance to the Decepticon leader Galvatron and in the year 2011 they joined the Decepticons in a massive assault on Cybertron to seize control of the Cybertronian supercomputer Vector Sigma so they could use it to establish Decepticon control over Cybertron.
After the death of Scorponok, Mindwipe and the other Decepticon Headmasters were forced to flee Earth.