Sabretooth was a mutant who believed that as men were crueler than less evolved animals, mutants should naturally be crueler and more monstrous than men. He was recruited into Weapon X, a black ops section of S.H.I.E.L.D. Initially coerced into serving them (he once spent six months as a N.A.S.A. crash test dummy for disobeying orders), he eventually took a sadistic liking to the work, gaining a degree of authority over his fellow captive mutants. Sabretooth instantly disliked the similarly powered Wolverine, and has made an unverified claim that he slew Wolverine's wife and child.When Wolverine escaped Weapon X, Sabretooth was sent to bring him back; they clashed with one another in the New York subway and in Times Square before Wolverine escaped, thanks to Spider-Man's help.

After Wolverine joined the X-Men, Weapon X located their Mansion base and attacked it, capturing all of them except the absent Wolverine. Weeks later, Wolverine was recaptured in St. Petersburg. Sabretooth, now enhanced with adamantium implants similar to but more extensive than Wolverine's, took Wolverine outside the base to torment him by destroying files detailing the amnesiac Wolverine's past in front of him, unaware his rival had allowed himself to be captured so that Weapon X's location could be uncovered. A tracker implant within Wolverine led the Brotherhood of Mutants to the area to free the X-Men. Wolverine tricked an enraged Sabretooth in to cutting his bonds, and the two battled until Wolverine castrated his foe and tackled him off a cliff. Wolverine recovered consciousness first, doing unspecified but non-lethal damage to his downed foe.

After Sabretooth recovered, he joined the terrorist Brotherhood of Mutants. Though he briefly quit in disgust over Quicksilver's weak leadership, he returned when Magneto resumed control, soon becoming his right hand man. He led raids on the Louvre and other museums and galleries, gathering art prior to Magneto's plan to devastate the Earth. He also oversaw missions recruiting oppressed mutants from around the globe. When the X-Men attacked the Brotherhood's Citadel, Sabretooth again clashed with Wolverine, boasting he was bigger, stronger and could heal any wound Wolverine inflicted; in response, Wolverine decapitated him.

Sabretooth recently resurfaced, attacking Wolverine and Storm on a night away from the mansion and explaining that enough strands of his tissue were intact that his healing factor was able to reattach his head to his body. Sabretooth also claimed to be Wolverine's son, although the veracity of these claims are in doubt.