Set about five hours after the events of the film, Wesley Gibson continues his transformation into a full-fledged assassin and heir to a legacy of a secret fraternity of assassins. He continues his quest with a new mission to seek out the French chapter of The Fraternity, to hunt down The Immortal, and finally discover the truth about his family.
Wesley practies the basic abiliities and skills used in the game.
The story begins with Wesley having a recurring bad dream that ends the same way; with a mysterious killer that murders Wesley's mother. He wakes to find that his apartment has been breached by a team of assassins disguised as SWAT soldiers. They ransack Wesley's apartment and finally come upon a picture of his mother, Alyse. Breaking it, they find a decoded Kill Order in its frame. After hunting down these intruders, Wesley confronts Araña, an assassin sent by the Barcelona Fraternity. Pekwarsky, the Fraternity's master bullet-maker arrives and drives Araña off. He informs Wesley that he is the primary target on the Fraternity's black list. He also tells him that it will dispatch its minions to the recently destroyed Chicago Fraternity in order to collect the Loom of Fate.
Wesley learned to curve bullets and use adrenaline.
Cross first has to guard Alyse, who has recently given birth to Wesley. However, he fails as the Immortal shoots her and he barely escapes with the baby alive.
Wesley uses this tip make a return visit to the wreckage of the Chicago Fraternity Textile Mill, the place he destroyed in the movie. Inside, he confronts The Russian, who notices that Fox's body is gone. Wesley kills him, and noticing a binary code on his arm, he severs it for further inspection. Pekwarsky tells him that The Russian was one of the Guardians sent to collect the Loom. Three of these are sent from various Fraternities and their codes reveal the place where they intend to move the Loom. He also informs Wesley that he is meeting a buyer by the name of Brummel who ordered a crate of bullets that have been engraved with Wesley's name.
The third tutorial.
Later, on a mission to kill a member of the Fraternity given to him by Sloan, Cross engages The Immortal on an airliner, which was only serving as a trap as The Immortal takes the last parachute. Cross then works his way out of the burning airliner and escapes in a parked red Dodge Viper.
Wesley secretly tags along with Pekwarsky and kills Brummel, taking his piece of the code as well. However, Wesley notices that Pekwarsky is holding something back - Pekwarsky is really after the Kill Order that was taken at the beginning of the game.
After Cross returns to the Chicago Fraternity, he confronts Sloan for giving him a false Kill Order and framing him as a rogue assassin. Before the two can quarrel, the Paris Fraternity invades the Chicago Fraternity looking for Cross. During the fight, he discovers a Kill Order for Sloan and realizes his treachery. However, Sloan turns Cross'S comrades against him and Cross is forced to flee. The Immortal chases him and in a duel with him, Cross fires a bullet straight into the Immortal's gun which explodes, severely damaging the Frenchman's face.
Wesley kills Araña and takes her Binary Code. He then descends into the crypt and finds his father's mummified body. He takes the Fire Eater guns from his hands and promises him that he'll take care of the Immortal.
Back in the present, Wesley heads to confront the Immortal.
However, just before they have a final duel, the Immortal reveals a twist; it was Cross who killed Alyse, with the two lovers mutually agreeing that following the Code was the only way it could end. The Immortal was merely sent to kill Wesley, who was considered an abomination by the Code. After defeating the Frenchman, Wesley has a philosophical dialogue with the Immortal. The latter says that even though Wesley's parents were fanatics, they put their faith in the Loom, and that no great human endeavour was ever achieved without faith. Wesley has had enough, and fires the bullet with Wesley's name on it at the Immortal, ending his life.
- Endings vary depending whether the PC or the console version of the game is played. On the console, it ends with Wesley killing the Immortal while on the PC, it ends with the bullet missing the Immortal's head and Wesley urinating in his face.
- The cover art for the game was based on the original cover of the 1st Issue of the comic series, while the text style is from the cover of the film.
- The Killer Suit's goggles featured on the PC version's cover are colored blue, while on the console versions' cover, they are red.