The youth who would eventually be called the Ancient One was born over five hundred years ago in Kamar-Taj, a village in a hidden land in the Himalaya Mountains in the area now known as Tibet. Originally, the youth, like the other men of the village, was a peaceful farmer. However, an older fellow villager named Kaluu somehow gained certain magical knowledge, which he shared with the youth. Kaluu and the youth began exploring the secrets of sorcery together, and learned how to harness mystical energy for their own uses. However, their motives were quite different. Kaluu intended to build a vast empire, while the youth wished to use sorcery to benefit his fellow villagers. While the youth continued his studies, Kaluu slowly used his sorcery to influence the villagers' minds. Eventually, Kaluu and the youth together cast a spell that eliminated disease, poverty, and suffering from Kamar-Taj, and granted its people immortality. Shortly thereafter, the people of Kamar-Taj, responding to Kaluu's magical influence on their minds, crowned him as their king. For over a year Kaluu organized the men of Kamar-Taj into an army of conquest, while slowly increasing his magical control over the minds of the people of Kamar-Taj so that they became no more than his placid puppets. The youth attempted to warn the villagers about Kaluu, but Kaluu's magic prevented them from heeding him. Kaluu struck the youth from behind with a mystical bolt which paralyzed him. Then Kaluu had his soldiers conquer a neighboring village and reduce its people to slavery.
While Kaluu plotted further conquests and the people of Kamar-Taj fell into decadence, the paralyzed youth, whom Kaluu had placed in the public square as an object of ridicule, mentally called upon mystical forces to defeat Kaluu. However, the youth was not yet a full master of the mystic arts, and, although hr did not intend it, the mystic forces he summoned creates a pestilence that wiped out virtually the entire population of Kamar-Taj. Kaluu fled to another dimension. With Kaluu gone, the youth was freed from his paralysis. Ironically, Kaluu's spell had protected the youth from the full effect of the mystical pestilence: the youth was no longer immortal, but he would now age at a very slow rate, so that he would nor reach the end of his life span for five centuries.
Because of what he had witnessed in Kamar-Taj, the youth left the village in order to devote his life to combating other evil sorcerers. To this end, the youth sought out an ancient order of sorcerers whose elder members were known as Ancient Ones, and which was dedicated to protecting Earth's people from black magic. The youth continued his mystical studies with them, and rapidly became far more skilled in sorcery than his colleagues. His prowess was so great that he was the first Earth mortal to meet with Eternity, the sentient embodiment of the life forces of the universe, who presented him with the Eye of Agamotto, the Earth dimension's very first sorcerer supreme. The amulet enabled its possessor to protect his or her dimension from the sinister extradimensional entity known as Dormammu, and using it, the man who became known as the Ancient One kept Dormammu out of the Earth dimension for nearly five centuries, although he never succeeded in entirely defeating Dormammu. Through this and other feats, the man who became known as the Ancient One became recognized as the sorcerer supreme of the Earth dimension. The Ancient One further increased his knowledge even within the last century by traveling back in time to ancient Babylonia, defeating the gryphon whom the priests of the Babylonian god Marduk had set guard over the Book of the Vishanti, and thus obtained the book, the greatest known source of "white" magical knowledge.
Within the last several decades, the Ancient One, who had outlived all the other members of his order, was approached by Baron Karl Mordo of Transylvania, who wished to become his pupil. The Ancient One was nearing the end of his long life and realized he needed a successor. Although he recognized Mordo's evil ambitions, he also sensed Mordo's talent for sorcery, and he decided that he could at best convert Mordo to the service of good and at worst keep him in check.
Sometime later, a gifted but somewhat amoral surgeon, Doctor Strange, sought out the Ancient One to cure his hands, which had been injured in an automobile accident in a way that prevented him from holding his surgeon's tools with the complete steadiness that was necessary to perform surgery. While staying at the Ancient One's palace in the Himalayas, Strange learned that Mordo was plotting against the Ancient One. Mordo placed a spell upon Strange which prevented him from warning the Ancient One about Mordo, but the Ancient One freed Strange of the spell and assured him that he was aware of Mordo's evil nature. Having witnessed the power of good and evil magic in action, Strange found a new, higher purpose in life, and became the Ancient One's disciple. Mordo left the Ancient One's tutelage sometime afterwards to embark on his career of evil. Dr. Strange, on the other hand, remained with the Ancient One for years, proved to be highly talented in the mystic arts, and eventually became the Ancient One's successor as sorcerer supreme.
Some years after Doctor Strange had left the Ancient One's palace to return to New York City, the Ancient One and Dr. Strange fought the powerful demon Zom at Stonehenge in Britain. Knowing that he could not long withstand Zom's power at his advanced age, the Ancient One made it appear as if Zom had killed him by fusing his body with one of the Stonehenge monoliths. As he seemed to die, the Ancient One claimed to transfer his magical abilities to Dr. Strange; instead, the Ancient One actually activated potential for further magical ability in Dr. Strange that had until then remained latent. Zom was imprisoned by the Living Tribunal, and the Ancient One, still in possession of his powers, was reunited with Dr. Strange some days later.
In recent years, Doctor Strange inherited the title of Sorcerer Supreme, having achieved in mere decades the skill level it had taken the Ancient One almost two centuries to reach. The Ancient One continued to advise Strange as necessary and tended to by the last of his servants, Hamir, occasionally aided by Strange against enemies, including Kaluu.
However, when the demon Shuma-Gorath sought to enter the Earth dimension via the Ancient One’s mind, the Ancient One prompted Strange to kill his physical body rather than allow Shuma-Gorath passage. Although physically dead, the Ancient One has since manifested in astrial form in both the present and the past for various purposes.