As En Sabah Nur grew, he surpassed the other tribesmen in intelligence and strength. Everyone in the tribe except for Baal hated and feared him for his inhuman looks and great abilities. Nur did not understand their fear, but hardened his heart against it. Moreover, he believed in the principle that Baal and the tribe lived by, that only the fittest, tested by hardship, would, and should, survive. On the day of his tribal rite of passage into manhood, the seventeen-year-old En Sabah Nur killed three armed warriors of the tribe using only his bare hands.

At this time Egypt was ruled by Pharaoh Rama-Tut. On the day of En Sabah Nur's rite of passage, Baal explained to him that Rama-Tut was no god, as most believed, but a man, who had arrived in a strange vessel. Years ago the tribe had stumbled upon the time-traveler's crashed ship, taken the injured man back to their camp, and nursed the injured and temporarily blinded man back to health. One night he wandered away, taking with him objects the tribesmen had brought from his vessel. Weeks later, his sight restored, Rama-Tut returned, wielding weapons of devastating power and leading the Egyptian army. He massacred the tribe and enslaved the survivors. Although he tortured them, no one revealed the timeship's location.

In actuality, Rama-Tut was a time traveler from the far future who would later become known as Kang the Conqueror. Kang knew that Apocalypse, one of the most powerful mutants who ever lived, and the one who was destined to rule the world, had been born in ancient Egypt. Hence, Rama-Tut had gone back in time to find Apocalypse as a child, raise him, and thereby become the master of the most powerful being on the planet.

On the day of his rite of passage, Baal brought the young Nur to a sacred cave whose entrance became blocked by a cave-in, trapping them underground. After a week of wandering without food or water, they found the remnants of Rama-Tut's timeship within an underground Egyptian tomb. Baal told Nur that he believed him to be a conqueror whose coming was foretold in ancient prophecies, and that Nur was destined to overthrow Rama-Tut. Then Baal died from lack of nourishment, and Nur, whose mutant physiology kept him alive, vowed to take vengeance on Rama-Tut and claim his destiny. Four weeks later he finally made his way back to the surface.

Nur became a slave, but eventually he had a vision of the Egyptian death god Seth, who urged him to become a conqueror. It was at this moment that Nur first manifested his superhuman powers. Eventually, at a time when many time-traveling super-heroes, including the Fantastic Four, the West Coast Avengers, and Doctor Strange arrived in Rama-Tut's Egypt, the Pharaoh finally came face to face with En Sabah Nur. Rama-Tut offered to make him his heir if he would swear his loyalty, and then tried to kill him when Nur refused. Nur defeated Rama-Tut's warlord Ozymandias and Rama-Tut, who finally escaped back into the future, eventually to take on the identity of Kang.

From then on Apocalypse plotted the conquest of the planet through bringing about wars and conflict, in which the strong would defeat and destroy the weak. Over the centuries he was worshipped by many civilizations under a variety of names. Mutants, he was certain, would one day rule the world, with him as their leader, and so he waited. Most of what Apocalypse did during these centuries is as yet unknown.

At the time of the Crusades, Apocalypse arranged for the warrior Bennet du Paris to activate his latent mutant powers for the first time. Renaming him Exodus, Apocalypse made him his servant but later cast him into a deathlike trance when Exodus rebelled against him.

In 1859, Apocalypse awoke from centuries of hibernation in an underground chamber in London. It was then that he first met Dr. Nathaniel Essex, who believed that through selective breeding of humans, he could bring about the rapid evolution of superhuman mutants. Apocalypse offered to transform Essex into a long-lived superhuman being himself to give him the time to further his research, but at a cost: his servitude. Essex accepted, and Apocalypse transformed him into Mister Sinister. However, the Askani, a clan of rebels against Apocalypse two thousand years in the future, transported Scott Summers and Jean Grey-Summers, also known as Cyclops and Phoenix, to 1859. There they prevented Apocalypse from assassinating Britain's Queen and Prime Minister.

Apocalypse, temporarily weakened by a virus with which Sinister had infected him, went back to waiting for the proper moment to reemerge. It came a century later, when in a short time the world became populated with a new race of superhuman mutants. Apocalypse first reappeared as the employer of the Alliance of Evil, a team of mutants who battled the original X-Factor. X-Factor was a group comprised of the original members of the X-Men.

Subsequently, Apocalypse began recruiting a team of mutant agents he called his Horsemen. Apocalypse rescued Warren K. Worthington III, alias the Angel, from death and manipulated him into serving him as the Horseman named Death. Worthington's wings had been amputated, but Apocalypse used his advanced genetic engineering techniques to give him new wings with metal-like feathers. Eventually, however, Worthington forsook Apocalypse and returned to X-Factor, and then to the X-Men.

Later, Apocalypse infected the infant son of Cyclops and Madelyne Pryor, Nathan Summers, with a techno-organic virus, having recognized that if this child grew up he would be powerful enough to defeat him. The Askani once again stepped in and brought the child to their own time period, two thousand years in an alternate future.

In the present day Apocalypse continues to conspire to rule humanity. In the alternate future in which the Askani live, Apocalypse has finally ascended to power. He became aware of the young Nathan's presence in that time, but only succeeded in kidnapping a clone of the child which the Askani had created. Not knowing this second child to be a clone, Apocalypse ceased his hunt for the real Nathan. Raised under the tutelage of Apocalypse, the clone grew up to become the terrorist Stryfe. By this time Apocalypse had to transfer his mind and powers into host bodies in order to stay alive. Since his current body had grown old and feeble, Apocalypse planned to transfer his consciousness and power into Stryfe's.