In the Age of Apocalypse, the Eternal One rose in the modern era much earlier than in our timeline. His aggression and drive at the outbreak of mutantkind brought Sinister back under Apocalypse’s patronage, becoming the longest serving Horsemen of Apocalypse. Through Apocalypse’s conquest of America, Sinister was able to serve his master and his own ends by developing the genetically advanced soldiers of the Infinites and the Madri through his experimentation. Always interested in mutant bloodlines, Sinister populated his Elite Mutant Force with Alpha mutant siblings to study variations in the X-gene, including his own adopted sons, Scott and Alex Summers.
As before, though, Sinister eventually desired freedom from Apocalypse’s yoke. He combined the genetic material of Scott Summers and Jean Grey to produce a boy named Nathan, possessing vast psionic potential that made him a powerful weapon to turn against En Sabah Nur. Sinister hid his creation in the Pens, but lost track of Nate during an escape. Forced to take an active hand, Sinister abandoned his master to hunt down his weapon. In the guise of “Essex,” Sinister infiltrated Forge and his band who were looking after Nate on the road. Essex drew Forge’s suspicions by pressing Nate to stretch the limits of his powers and was forced to kill Nate’s protector. This led to open warfare between Nate and Sinister, and Sinister was apparently killed at the end of their duel.
Sinister survived, however, saving Jean Grey for himself and going underground to continue his experiments. He was eventually discovered in the new order led by Magneto and Weapon X. Sinister unleashed the Phoenix along with his Sinister Six to battle the X-Men. Jean broke free of Sinister's control, however, and her Phoenix Force combined with an attack by Logan and Kirika seemed to finish him off for good.
Ultimate Sinister originally appeared to be an insane serial killer, using telepathic powers to dominate his victims before shooting them. Sinister believed his killings were sacrifices to satisfy a voice in his head, Lord Apocalypse. Seemingly delusional, Sinister eventually completed his sacrifices and physically transformed into Apocalypse, suggesting the “voice” may have been a genuine entity all along. The Phoenix Force defeated Apocalypse and regressed him back into Sinister. Essex later operated with the RoXXon Brain Trust with several other scientists and free thinkers. Sinister was last seen manipulating several figures by using his telepathic powers to pose as ghosts of influential people from their lives, encouraging them to fulfill his needs. He had returned to the worship of Apocalypse, raising further questions about that entity’s existence.
In House of M, Mister Sinister was observant enough to recognize the regular path of mutant evolution had accelerated. The House of Magnus ruled a largely mutant population much larger
than his estimates would have predicted for decades. Perturbed at being left behind, Sinister did the only thing he knew how to do and genetically engineered a mutant child named Nathan from DNA he surreptitiously acquired. He hoped the child would be grown enough to serve as a bridge between human and mutant when Magneto passed his firm rule on to his less-tested children.
On Battleworld, one domain was Bar Sinister of the Baron Sinister. The baron was a rogue who challenged his neighbors and skirted the law of God Doom himself. After capturing Carol Danvers of the pre-existing Earth-616, he amused himself with assisting her in rebellion against the throne. During an invasion of Castle Doom by dissident forces, Sinister and his clones betrayed Doom and began attacking his loyal barons. He was decapitated for his treachery, but that was hardly a deterrent for the mad geneticist.
In other domains, Sinister fulfilled similar roles to ones he had taken in the past. In the Domain of Apocalypse, Essex continued to serve as a loyal Horseman until the Legacy Virus threatened to destabilize all mutant powers. Sinister instead restored the Phoenix in Jean Grey, who purged the mutant gene from that domain. In Inferno’s domain, Sinister was trapped for five years behind a force field containing the Limbo demon outbreak in Manhattan. On the run from the Darkchild and his own ungrateful creation Madelyne Pryor, Sinister captured the X-Man Boom Boom and cloned a mutant-demon hybrid army of incendiaries from her. However, he was killed when the Goblin Queen turned Boom Boom against her own manipulator.
In X-Men: The End, Mister Sinister’s origins were retold entirely. This Sinister learned that while he aged more slowly after Apocalypse’s changes to his cellular structure, he still aged. Through an ever-advancing cloning process, Mister Sinister created younger copies of himself every few decades and transferred his mind into them to stave off death. Sinister eventually wanted to be fully free of Apocalypse’s influence, though. He maintained genetic samples of Nathaniel Essex before his transformation and altered them with an X-Gene and mutant energy-generating powers based on young Scott Summers. Sinister hoped to have both power and independence from his master, but Apocalypse anticipated these maneuvers and had the infant clone abducted by the Thieves Guild of New Orleans, leading to Sinister’s copy being raised as Remy LeBeau and becoming Gambit of the X-Men.
Decades passed, and Mister Sinister remained a hunted foe of the X-Men. He kept a secret base in Genosha, under Charles Xavier’s nose, and seized full control of Weapon X and the Neverland camp, which he moved to the Blue Area of the Moon for safekeeping. Sinister traded with the Slavers and became aware of movement happening in the Shi’ar Empire, and Warskrulls hunting X-Men. Sinister called in an old marker from Gambit, forcing his unwitting son to kidnap his own children with Rogue, and the children of Cyclops and Emma Frost. Sinister wanted this prime genetic material of the next generation out of the way when the alien forces struck the Mansion. Sinister finally took the time to explain Remy’s origins to him, trying to convince his “son” to become a willing partner. He failed and had to deal with attacks from without and within, as Gambit freed his children and Rogue stormed the base. Using his natural similarity to Gambit, Sinister posed as his son long enough to get close and mortally wound Rogue. He was killed in turn shortly thereafter by Mystique, but the deed was done.
In X-Men Forever, different events unfolded after the X-Men’s first battle with the Acolytes. Mister Sinister received another new origin as well – an immortal mutant, trapped in the body of a pre-
adolescent boy, Nate Essex used his artificially constructed avatar as Mister Sinister to intimidate others. When the phenomena known as “burnout” threatened the mutant race, Essex feared he would suffer first as one of the oldest surviving mutants. He thought his namesake, the son of Cyclops, might hold the key to preventing his early demise. Mister Sinister sent his Marauders to kidnap Nathan Summers, but the X-Men and Starjammers prevented it.
The Mister Sinister of Mutant X was very similar to his main counterpart, obsessed with the Summers genetic line. His genetically-engineered Madelyne Pryor married Havok in this reality, producing a young Scotty Summers. Sinister also created a boy-girl pair of twins from Grey-Summers genetic material. They were stolen from him for a time, but he commissioned the thief Gambit to retrieve them. Sinister declared the girl was surplus and could be disposed of, but
Gambit refused and adopted her as his own daughter, Raven. The boy remained with Sinister, who age-accelerated him into the teenaged X-Man. Sinister was allied with the insane Charles Xavier who wanted Scotty, Nate and Raven as psychic batteries for his powers. Even Sinister was shocked when Xavier declared his plan to merge the minds of every person on Earth into his and fought back. Xavier was too powerful, however, and struck down the rebellious Sinister.
In Earth X it was revealed that Mister Sinister was actually an identity taken by Colossus, the result of an unexplained time travel paradox. Like Nightcrawler being Belasco, this was one of several paradoxes instigated by Mephisto to propagate the multiverse for his own nefarious ends.
In What If? (2nd series) #37, most of the X-Men had been turned into vampires prior to Inferno, and Wolverine now ruled as lord of the vampires after slaying Dracula. Mister Sinister felt his own plans were spiraling out of control, and so he planned to acquire the Darkhold from the Sanctum Sanctorum of the late Doctor Strange. The Montesi Formula within its pages would give him the power to eradicate all vampires on Earth. Just then, however, the Dread Dormammu teamed up with the Goblin Queen and unleashed the demons of Limbo and the Dark Dimension on Earth. Instead of killing the vampires, Sinister pledged to use the power of the Darkhold to empower them with enough strength to defeat the demons, in exchange for the mutant vampires accepting exile to another plane. Wolverine and the X-Vampires agreed and were successful, leaving Sinister free to repopulate the mutant race with non-vampire clone samples from his own storages.
In What If? (2nd series) #74, the timeline diverged back when Scott and Alex Summers were still residents of Mister Sinister's orphanage. Instead of killing the Bogarts before they could adopt Scott, Sinister subtly manipulated them into backing out of the adoption. This drove Scott deeper into his control, avoiding the event which led to Scott running away and being recruited to the X-Men. Mister Sinister created his own "X-Men", indoctrinating Cyclops and Havok into his version of "the dream", fighting alongside Sabretooth, Sauron, and Malice (possessing the body of Madelyne Pryor). Sinister arranged for his X-Men to encounter Xavier's X-Men, complete with Jean Grey leading the opposite team of youngsters. Playing on Scott's doubts, Sinister next orchestrated his own "death" at Magneto's hands, because Scott lingered with Jean instead of responding to Sinister's cries for help. Sinister's passing completed Scott's programming, convincing Cyclops and Havok to infiltrate the X-Men when Xavier invited them to join, only to tear them apart from within, all while Mister Sinister watched from the shadows.
In Old Man Logan’s future, Mister Sinister was responsible for the plan used by the villains to overthrow the country and destroy the heroes. Left out in the cold by the Red Skull, with no territory to call his own, Sinister made do with what he had. He reconnected with Sabretooth and tried to restart the Weapon X Program. Sinister had his agents hunting Logan, Danielle Cage, and the last son of Hulk to add to his genetic stores. There was a fight at Hammer Falls, the point where Mjolnir fell to Earth, never to be raised by Thor again. Danielle Jones proved worth of the hammer’s power and used it to slay Sinister.
Spider-Man: Renew Your Vows was a timeline where Spider-Man’s wife and daughter joined him
web-slinging as Spinneret and Spiderling. Mister Sinister was active in this timeline pursuing his genetics work disguised as Doctor Vardia with OsCorp while also hunting rare genetic samples in disguise as Doctor Krikos. After an encounter with the Spider-Family, Sinister used a genetic sample from Spiderling to empower Chelicera and other spider-enhanced henchmen for his own work. Eventually, he grew an entire army of spider entities to attack the X-Mansion but was driven off by the X-Men and Spider-Family.
Not much is yet known about the Mister Sinister of Moira IX’s timeline, only his works. However, it can be assumed he was brilliant, self-serving and treacherous. In the war with the Man-Machine Supremacy, mutant leadership authorized the opening of Sinister’s breeding pits on Mars. Once he perfected the growth of fodder clones for the army, Sinister moved on to second- and third-generation clones from his breeding program. These Chimera mutants had a few as two and as many as five X-genes amalgamated together in endless variations. The fourth-generation was a step too far, though, attempting to produce Chimera Omega-class mutants in a disastrous experiment that killed 40% of the mutant race and Krakoa itself before the Omega Chimeras destroyed themselves and Mars. Rather than being a failure, it appears the Omega Chimeras were designed to sow chaos as Sinister defected to the Supremacy… and was publicly executed for his troubles regardless.