When Spider-Man heads to Hell's Kitchen, Wolverine jumps at him but misses, he then tells Spider-Man that he doesn't smell right and that he is one of the symbiotes, so he fights him since he doesn't trust him, during the fight. Wolverine would ask Spider-Man some trivia questions to see if he really is Spider-Man (if the player answers the questions right. Wolverine will start to believe that he is Spider-Man, if the player answers wrong or decides not to answer them at all, it doesn't get Spider-Man anywhere), during the fight, hidden symbiotes would show up, (if Spider-Man fights the symbiotes, Wolverine would start to trust Spider-Man, but if Spider-Man fights him and ignores the symbiotes or lets Wolverine kill a symbiote, then it doesn't help). After the fight, on the good path, Wolverine figures out that he is not only irritating; he is Spider-Man, but then threatens Spider-Man that when the symbiote takes control over him, gutting is still an option. In the bad path, Spider-Man would tell Wolverine that they can keep fighting or he could help him, Wolverine then says that he guesses Spider-Man can control the symbiote, and tells him to use it, and Spider-Man tells him to help him locate the symbiotes. Wolverine says he will try but then threatens Spider-Man, saying that when the symbiote takes control over him, his life is over. Wolverine tells Spider-Man to use the black suit and use his Spider-Sense to locate the symbiotes; they find some symbiotes by doing this and defeat some; after they defeat enough, Wolverine tells Spider-Man to try to sense more of the symbiotes.
After Spider-Man defeats enough of them, he meets Wolverine again; Wolverine tells him that he did a good job, and Spider-Man then tells him that they need to find the source of these things. He believes Venom is behind this and then suggests that they should split up and find him later on during the symbiote invasion. Spider-Man meets Wolverine at a church. Wolverine finds out the weakness of the symbiotes and that they can use the bell to stop them. Spider-Man and Wolverine then fight off the symbiotes, and eventually, a S.H.I.E.L.D. hovercraft shows up to evacuate the civilians, Wolverine tells them to go. Spider-Man and Wolverine get on, but then the symbiotes manage to grab the hovercraft; Wolverine then jumps at them to stop them; unfortunately, the symbiotes bond to Wolverine, turning Wolverine into Symbiote Wolverine, under the influence of the symbiote. Wolverine tries to kill Spider-Man, and Spider-Man tries to tell him to fight the symbiote, but it is not working. During the fight, Wolverine gets armor, later on, tries the church bell at Spider-Man but fails. Spider-Man does defeat Symbiote Wolverine (in the good path, Wolverine fights the symbiote and gets it off of him, then says this is who he is. In the bad path, Spider-Man lifts up Wolverine, then rips him in half, and the symbiote comes off. Wolverine then tells Spider-Man that he will kill him for this). in the good path, Wolverine is last seen on top of the S.H.I.E.L.D. Helicarrier fighting the symbiotes alongside Luke Cage and Moon Knight. In the bad endings, S.H.I.E.L.D. gets Wolverine, Black Widow asks Wolverine if he is in full control of the symbiote, Wolverine then says yes, Black Widow then tells Wolverine to bring her Spider-Man, dead or alive, Wolverine goes with dead.