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The Creators were a group of sorcerers who ultimately became near-omnipotent cosmic entities and major antagonists to Doctor Strange.
The Creators are a league of sorcerers from different time periods on Earth (ranging at least as far back as the Pre-Cataclymic Era). Their exact origins are unknown, but they gathered together with the goal of transforming themselves into stellar bodies, taking over the forms of the stars, and transforming the current/previous stars into human form. The reason for this is that, at least in the Marvel Universe, the stars are the original source of all energy in the universe, including mystical. By taking over the power of stars, they would gain virtually unlimited power and be able to control the entire universe.
The Creators saw Dr. Strange as one of their strongest potential opponents.
The Creators became allied with the In-Betweener, who powered the creation of the Cosmic Wheel of Change. Using the Wheel, they began their plot to replace the stars. Stars they replaced could be identified as blue dots in the sky.
The Creators brought the being known as Xander to their realm, where they trained him in magic, and in other forms of combat.
The Creators (and Xander) apparently manipulated the Ancient One, causing him to strip Dr. Strange of the title (and power) of Sorcerer Supreme.
Xander attacked Dr. Strange and Clea. Although Strange defeated Xander, he did manage to cast a spell causing Clea to behave malevolently for some time. The Creators recalled Xander to Creation II.
Clea rampaged through the city until Dr. Strange managed to remove the spell that Xander had placed on her.
Dr. Strange journeyed into the Quadriverse to investigate the reason for Xander's attack. He attempted to save the "Guardian" of the Quadriverse from imprisonment, but learned that the nature of the realm was to have one Guardian imprisoned at all times. After freeing one, she/it was replaced by another.
As Dr. Strange passed through the final portal into the realm of the Creators, they awakened Visimajoris to stop him. Strange was saved from Visimajoris by Apalla, who was a star that had taken humanoid form in an effort to stop the Creators' plot. Strange and Apalla confronted and battled the Creators, and Apalla located the Cosmic Wheel of Change. Strange was suffering from some type of malady that was making him act rashly, and he destroyed the Wheel, with the intention of stopping their plot. However, this did not stop them, but rather allowed them to rewrite reality as they saw fit. Without the Wheel, there was no way to reverse their changes.The Creators accomplished their goal, taking the forms of stars and casting the real stars into humanoid form. The now-humanoid stars were comatose after the transformation, and Strange placed them in stasis around the star which was once Alpha Centauri.
Strange returned to Earth to find it over-run by chaos, with semi-human creatures running rampant. He entered what was once his Sanctum Sanctorum and found it inhabited by the Creators' replacement of him—Dr. Stranger Yet. With the aid of Clea and Wong, Strange incapacitated and imprisoned his would-be replacement.
Strange learned that the Creators had cast the Ancient One back into human form, and that he was living as a drunk in the Bowery of New York. The Creators sent four unnamed agents to attack Strange and the Ancient One, who defeated them. The Ancient One directed Strange to confront the In-Betweener.
After encountering the In-Betweener, Strange located the reformed Cosmic Wheel of Change, which was guarded by his enemy, Stygyro (who now, as one of the Creators, possessed the power of a star). Strange managed to defeat Stygyro, but then the In-Betweener reappeared, refusing to allow Strange to reverse the Creators' changes.
Strange called on the power of the In-Betweener's creators, Lord Chaos and Master Order. Using power granted by them, Strange temporarily defeated the In-Betweener and reversed the Creators' changes in the Universe. The stars were returned to their rightful forms and location, Earth was back to normal (as much as it can be), the Ancient One again became one with the universe and all was right with the world.