Logan, também conhecido como Wolverine, é um mutante com poderes regenerativos, três garras de aço em cada mão e cujo esqueleto é permeado com um tipo de metal chamado adamantium. Nessa nova produção, o personagem criado por Stan Lee ainda não faz parte da escola de mutantes e quer buscar os segredos de seu passado, contando com a ajuda de Charles Xavier.

In 1845 in North-Western Territory, British North America, young James Howlett (Troye Sivan) sees his father John Howlett (Peter O'Brien) killed by his friend Victor Creed's father, Thomas Logan (Aaron Jeffery). In an act of vengeance, James kills the elder Logan using bone claws which have grown out of his hands. With his dying breath, Logan tells James that he is also his son. James and Victor (Michael-James Olsen) run away, pursued by a torch-wielding mob. They promise to look out for each other.

In the years that follow, adult brothers James (Hugh Jackman) and Victor (Liev Schreiber) are seen fighting together in the American Civil War, World War I, World War II, and eventually the Vietnam War. Their regenerative powers keep them from being killed in the battlefield. James is forced to act as a check on Victor's increasing rage and ferocity. In Vietnam, Victor kills a superior officer after being stopped from raping a girl, and James and Victor are sentenced to death by firing squad, though their unique regenerative abilities keep them alive.

Major William Stryker (Danny Huston) approaches the two mutants and offers them membership in Team X, his elite group of mutants. The team consists of mutants Fred Dukes (Kevin Durand), who's super-strong and invulnerable; John Wraith (Will i Am), who can teleport; Chris Bradley (Dominic Monaghan), a.k.a. Bolt, who can control electricity; expert marksman Agent Zero (Daniel Henney); and mercenary Wade Wilson (Ryan Reynolds), an amazing swordsman who never stops talking. The brothers join the group and are sent to the team's first mission: Invade the headquarters of a diamond trafficking operation in Lagos, Nigeria, to retrieve a meteorite. Afterwards, Stryker and the team brutally interrogate people from a nearby village to learn where the meteorite was found. James is disgusted by the murders committed by his teammates and abandons the group.