The Creation Matrix was left behind by Primus when he went into his slumber, and it became an icon of Autobot leadership. The Matrix passed from Prima to Prime Nova to Sentinel Prime, before passing to Optimus Prime. Prime held the Matrix, which was no longer considered a solid object but rather a spiritual one, during his time in stasis on Earth, and continued to wield it after reawakening in 1984.
Shockwave captured Prime after defeating the Autobots, planning to use the Matrix to create new Decepticon soldiers. However, Shockwave was also unaware that the Matrix was a solid object, and the Decepticon tried to draw the power directly from Prime's head. Optimus transferred most of that vestigal energy to Buster Witwicky, who developed fantastic powers to alter and control machinery. Thus, Shockwave could only force Prime to give life to the Constructicons. After Prime was restored, Buster returned the Matrix energies to him.
Prime later used the Creation Matrix to give life to the Aerialbots, but the energies were intercepted to create the Stunticons as well. When Prime was destroyed soon afterward, the Autobots unknowingly lost the Matrix, as it was still within Optimus Prime's body when it was launched into space.
The Creation Matrix remained dormant for a time, with the funeral barge crashing on the moon VsQs. After some time, the semi-sentient Creation Matrix touched a dying alien, a Deathbringer who eased suffering for those who died of incurable disease. The Matrix recreated him as a powerful being, whose purpose became corrupted- now he saw all life as a disease to be cleansed. The Deathbringer was destroyed by a revived Optimus Prime, but the Matrix hungered to experience more of the unfamiliar sensation of evil. It had its opportunity when another dying creature, a tiny insectoid predator, came across the Creation Matrix. It decided to recreate the creature and take it on as a new host, and the enhanced monster soon slaughtered an expedition sent to VsQs by the planet Cameron.
In the meantime, the Autobots had begun a Matrix Quest, seeking to find their lost lifeforce, and found competition in the Decepticon Thunderwing, who had an unusual affinity for the Matrix. Bumblebee (Transformers), Jazz and Grimlock found their way to VsQs around the same time as Thunderwing, and both sides began battling the Matrix-enhanced predator. The Matrix was torn between its current host and its affinity for Thunderwing, but in the end, it was taken by the Decepticon when he slew the monster.
Thunderwing used the raw power of the Matrix to decimate the Autobots on the Ark, until he realized it was using him as well, reveling in the commission of evil. When Thunderwing was damaged, the corrupted Matrix took full control, causing more destruction. Ultimately, Thunderwing and the Matrix were blown out an airlock. Drifting to a planetoid, the now-evil Matrix revived Thunderwing's body, and used its host to return to Cybertron. Once there, it attacked Unicron, who easily dispersed the lesser creature of evil. Optimus Prime reclaimed the Matrix, but it tried to possess him. Prime resisted, and with an effort of will, purged it of its newfound evil. He then took it within Unicron and unleashed its power, destroying the Matrix and himself.
Years later, the resurrected Prime had a new Creation Matrix; it was presumably given to him when the Last Autobot rebuilt him. This Matrix was stolen by Megatron, who used it to create new Decepticon troops (the Rotor Force and Laser Rods). It was later claimed by Starscream, who tapped its power to merge with the Decepticon Warworld. However, the now-incorruptible Matrix began to transform Starscream into a hero, a prospect so terrifying to Starscream that he was willing to surrender it back to Optimus Prime. The Autobot leader allowed the Swarm to consume him, knowing it would access the goodness of the Matrix- once it did, it was transformed into a creative force. The new Swarm recreated Prime once again before leaving.
Another Creation Matrix was passed to Ultra Magnus, then to Rodimus Prime. Presumably, this Matrix had been recreated by the Swarm. Rodimus Prime used the Matrix to imprison the essence of Unicron, only to have the Chaos-Bringer's essence gradually taint the object and Rodimus himself.
The Omega Point stories add another previous wielder of the Matrix, Primon, who came before Prima.
Originally, the Creation Matrix was conceived as a computer program, not a physical object, but that changed after the movie and during the U.K. series.