Mary Jane, whose career is floundering, is humiliated by Peter's changed personality and she finds solace with Harry. Urged on by a hallucination of his father, Harry regains his memory and blackmails Mary Jane to break up with Peter, threatening Peter's life. After Mary Jane tells Peter she is in love with another man (under Harry's direction), Harry meets with Peter and claims to be "the other guy". Later, Peter, wearing the black suit, confronts Harry and fights him. Harry throws a pumpkin bomb at Peter, who deflects it back, disfiguring Harry's face.
Under the symbiote's influence, Peter exposes Eddie Brock, a rival photographer at the Daily Bugle, by submitting doctored photographs showing Spider-Man as a criminal. Furious at having to print a retraction, J. Jonah Jameson dismisses Eddie. Meanwhile, the Sandman recovers from his injuries.
To make Mary Jane jealous, Peter brings Gwen Stacy, a woman Brock believes is his girlfriend, to the nightclub where Mary Jane works; Brock secretly sees them and assumes they are dating. Gwen catches on and storms out. Peter brawls with the bouncers and, after accidentally hitting Mary Jane, realizes the symbiote is changing him. He retreats to a church bell tower. While trying to remove the symbiote costume he hits the church's bell, weakening the alien and making it easier to remove. Peter tears the symbiote off and it falls to the lower tower, landing on Brock, who is praying for Peter's death. The symbiote transforms Brock into Venom and he accepts his new form. Venom finds the Sandman and offers to join forces in which he agrees.
Mary Jane hails a taxicab but Brock hijacks it and hangs it and a dump truck from a web hundreds of feet above a sand-filled construction site. Peter seeks Harry's help but is turned down. A crowd of people watch as Peter clashes with Brock. Harry learns the truth about his father's death from his butler and goes to help Peter. Harry temporarily subdues a gigantic incarnation of the Sandman, breaking him apart. Brock webs Harry's glider, causing it to bump into some pipes, making sonic vibrations that weaken the symbiote. Peter recalls the church bells weakening it previously. Brock tries impaling Peter with Harry's glider, but Harry jumps in the way. Peter forms a ring of pipes around Venom, creating a wall of sonic vibrations. The alien releases Brock, and Peter pulls Brock away from the creature, which can now live on its own. Peter throws a pumpkin bomb from Harry's glider at the symbiote, but Brock moves to re-bond with it and both are destroyed by the blast.
Marko reveals that he never intended to kill Ben, but only wanted his car and accidentally shot him when Dennis grabbed his arm, and says that Ben's death has haunted him since. Peter forgives Marko, who dissolves into sand and floats away. Peter and Harry forgive each other before Harry dies with Mary Jane and Peter at his side. Days later, Peter visits the jazz bar where Mary Jane is singing, and they begin mending their relationship.