HISTORY: The origins of the clandestine Weapon X Program date back to 1945 when a civilian advisor to the American military named Thorton investigated a liberated concentration camp and discovered the hidden laboratory of the enigmatic geneticist Mister Sinister. Using Sinister's research as the basis for his own work, Thorton, also known simply as the Professor, formed the Weapon Plus Program at the behest of the US government. Absorbing the resources of earlier projects such as Operation: Rebirth, which was retroactively, designated Weapon I, Weapon Plus was dedicated to creating super-soldiers. Over the next decade and a half, the Program went through various stages of development. The Weapon II and III Programs used animals as test subjects, while Weapons IV, V, and VI experimented upon various ethnic minorities. Beginning with Weapon VII, superhuman mutants became the preferred test subjects, a trend which continued from Weapon VIII through Weapon IX. The Professor remained active as a scientist throughout these incarnations of Weapon Plus, only to be repeatedly passed up for promotion.

By the 1960s, the Program had advanced to Weapon X and operated under the auspices of the Central Intelligence Agency. Several mutant operatives were organized as the covert operations unit Team X, including Wolverine, Sabretooth, Maverick, Wraith, Mastodon, and Silver Fox. The members of Team X were implanted with false memories by Psi-Borg, a telepathic ally of the Program, with the ultimate intent of suppressing their true memories and awareness of their abilities to become sleeper agents. A separate branch of the program, the Shiva Scenario, was designed to dispatch heavily armored robots to kill any operatives that went rogue. Team X members also received age suppression and healing factor treatments based on Wolverine's own mutant nature. By the early 1970s, Team X had been disbanded, with only Wraith and Maverick remaining in government service. The Weapon X Program continued operations under the cover of a division of the US Department of Agriculture.

Over a decade later, the US and Canadian governments were jointly administrating the Weapon X Program, with its Canadian branch in turn jointly operated by Canada's Department K and Department H. In this incarnation, Weapon X oversaw the enhancement of various Canadian government operatives, both human and mutant. One such operative was Wade Wilson, who received an artificial healing factor based on the one possessed by Wolverine. The Program was less than successful as most of the participants suffered from various physical or mental breakdowns and were sent to a special Hospice, where, unknown to the Canadian government, scientist Doctor Killebrew conducted inhumane experiments in his Workshop with his assistant, the Attending. Killebrew's activities were disrupted when Wilson, calling himself Deadpool, led a massive breakout; Canada eventually shut down its Weapon X branch.

Meanwhile, the US branch of Weapon X came under the direction of the Professor, assisted by Doctor Cornelius, Carol Hines, and the manipulative John Sublime. Guided by an unidentified backer, the Professor chose Wolverine as his first test subject. Logan was kidnapped and taken to a Canadian facility where he was subjected to a brutal process in which the near-indestructible metal Adamantium was bonded to his skeleton, including his mutant claws. The Professor was surprised at the full extent of Logan's mutant nature, which enabled him to recover from the process far more rapidly than anticipated. Reduced to a quasi-mindless state, Wolverine was sent to slaughter the inhabitants of the small town of Roanoke as a test of his abilities. He ultimately broke free of the Professor's conditioning and ran amok in the Weapon X facility. In the course of his escape, he slew most of the facility's personnel and savagely butchered a guard named Malcolm Colcord. Miraculously, Colcord survived, but kept his scarred face as a visual reminder of his hatred for Wolverine.

Logan was subsequently found by Department H's director James Hudson and his wife Heather, who nursed him back to health; he soon joined the Department as both an espionage agent and, later, a costumed operative. His memories of Weapon X clouded by memory implants and his own horrendous experience; he apparently did not recognize the significance of the term when, either by accident or design, it was used as his codename.

Despite the fiasco of Wolverine's escape, Weapon X continued under the Professor's guidance, while his associate Sublime moved on to later incarnations of the Weapon Plus Program. Eventually threatened with a shutdown, the Professor had Weapon X break all ties with Weapon Plus.

In recent years, Wolverine's memory of his manipulation at the hands of the Weapon X Program began to return, resulting in his being targeted by a Shiva unit. After fighting his way past the robot, he sought the Professor, only to find that he had been slain by Silver Fox, now a high-ranking operative of the terrorist organization Hydra. With his death, Weapon X was apparently abandoned, as Weapon Plus had long since superseded it. The Professor's associates, Cornelius and Hines, died shortly afterward at the hands of Maverick and Psi-Borg, respectively. Sometime later, Doctor Horatio Huxley attempted to revive Canada's Weapon X branch with a new test subject whom he exposed to deadly bacteria in hope of controlling the world, but after battling Canada's super-team Alpha Flight, the new Weapon X sacrificed his life to prevent the bacteria from spreading.

Meanwhile, Sublime, now the head of the Weapon Plus Program, contacted Colcord and encouraged him to lobby for the reopening of the US Weapon X Program. Colcord was successful, and became the Program's new Director with renegade S.H.I.E.L.D. agent Brent Jackson as his second-in-command. Colcord's plan was to openly recruit mutants, particularly those with disfigurements or poorly controlled powers, with the promise of treating them in return for their service in various field assignments.

Investigating the resources of the Program's earlier incarnation, Colcord discovered the means by which Wolverine had previously been mentally controlled, and directed his nemesis in stalking former operatives, who were either recruited or slain by Colcord's forces. Among the first to rejoin was Wolverine's nemesis, the feral mutant Sabretooth. Wolverine ultimately broke free of Colcord's control but was captured and held in a Program facility. He was freed by the mysterious mercenary the Shiver Man, and Colcord, unwilling to risk a further encounter, teleported himself and his staff away. Colcord subsequently recruited several other operatives for Weapon X, all of whom he equipped with implants preventing them from turning upon him or other high-ranking personnel. Colcord then opened the Neverland concentration camp, designed by the brainwashed mutant metalsmith Madison Jeffries, where mutants who were deemed useful were utilized as support staff and those who were not were executed.

Weapon X's activities came to the attention of the mutant time-traveler Cable, who organized an underground movement to oppose them. However, Jackson, betraying Colcord, manipulated Cable's resistance into storming the Weapon X facility, forcing Colcord to flee, only for Jackson to betray Cable's forces in return. Jackson was soon made the new Director, but he remained unaware that one of the scientists stationed at Neverland, Doctor Charles Windsor, was in fact a disguised Mister Sinister, ironically using this outgrowth of his past work to further his experiments.

Subsequently, Wolverine's current team, the mutant adventurers the X-Men, arranged for one of their members, Chamber, to infiltrate Weapon X. Accepted as a field agent, Chamber was assigned by Jackson to kill Sublime. Meanwhile, operative Agent Zero, the former Team X alumnus Maverick, turned renegade and began single-handedly targeting former operative Marrow's new, more violent version of Cable's underground. At the same time, Colcord, driven to madness by his situation, plotted an assault upon mutantkind with an army of Jeffries-built Sentinel robots. After Chamber went missing while seeking to discover the nature of Neverland's activities, Wolverine set out to find him but instead found the camp abandoned. Zero found the Weapon X facility similarly vacant, and both men joined forces with Fantomex, formerly Weapon XIII of the Weapon Plus Program, in search of answers. However, they found only Sublime, who had survived Chamber's attack, and the three barely escaped an attack by Sublime's mutated U-Men soldiers. Wolverine and Zero later defeated Fantomex after he was found to still be under Weapon Plus control.

Wolverine then found himself in conflict with an offshoot of Weapon X in pursuit of another former Weapon X experimentee, the female feral mutant called the Native. Aided by Sabretooth, who sought revenge on this group's leaders for their betrayal of him. Wolverine was able to rescue the Native. Escaping into the nearby woods, the Native was subsequently hunted down and slain by Sabretooth.