Spider-Man is sent through several dimensions trying to fix time and seal away Spider-Carnage. Peter meets his would-be girlfriend Gwen Stacy and Stan Lee.

Spider-Man goes after Eddie Brock for libeling him, as he is now being stalked by bounty hunters at every turn. After being reassured by Mary Jane that he has changed, he seeks help from Dr. Curt Connors who discovers that the suit is alive, and Peter is the host organism.

The Kingpin is furious at Spider-Man and sends the Shocker and the Rhino out to finish him off with the aid of another new invention of Alistair Smythe. Meanwhile, Eddie Brock, as the symbiote creature Venom, is busy playing cat and mouse with Spider-Man, intruding on Peter's private life and making it clear he knows the web-slinger's secret identity. To make matters worse, Peter soon realizes that the pumped-up Eddie as Venom is stronger than he is.

Spider-Man and Venom must put aside their differences and help Iron Man stop Carnage and Baron Mordo from releasing Dormammu.

Peter Parker and Mary Jane are finally a couple, but their happiness is short-lived as the Green Goblin, armed with a Time Distorter and the true identity of Spider-Man, seeks to destroy the web-slinger by any means necessary.

A space shuttle piloted by J.J.'s son, John Jameson, crash lands on the Tri-Borough Bridge carrying two strange meteors—one that could provide a new nuclear fuel and one that contains an alien substance. The first is stolen by the Kingpin's henchman, the Rhino, just as Spider-Man arrives to save Jameson and the co-pilots. When the Rhino sends the aircraft off the bridge, Spider-Man emerges from the water with a dark stain covering his costume. Exhausted, he heads for home, only to awaken hanging from a skyscraper, now clothed in a black version of his costume.

Under the psychiatric care of Dr. Kafka, Eddie Brock has come to believe that Venom is a figment of his imagination. Then Baron Mordo tempts Eddie to a reunification with the alien symbote that makes him as powerful as Venom.

Spider-Man finds himself in yet another dimension, where he meets himself.

Harry's father, Norman Osborn, disappears after an explosion at his chemical plant. Spider-Man's search for his friend's father, one way or another, meets with complications, namely an airborne fiend who calls himself the Green Goblin.

Spider-Man and Daredevil manage to recover the disk that can clear Peter Parker's name. However, when Matt Murdock hands the disk over to the FBI, detective Terry Lee discovers agent Choi may not be working for the right side when she hands it over to Richard Fisk. After learning that Aunt May is in the hospital, Peter risks his life to go visit her, but he and Mary Jane are kidnapped when the Chameleon disguises himself as Anna Watson. With Peter and the disk in the hands of the Kingpin, Daredevil must stop the criminal mastermind and clear Peter's name.

Spider-Man's progressing neogenic mutation is making him ill and he seeks the aid of a man known to help all mutants, Dr. Charles Xavier. In doing so he meets the X-Men, but is disappointed to learn that Xavier does not 'cure' mutancy, only helps those born that way to accept and control their abilities. In the process of this endeavor he becomes involved in a plot to destroy mutants everywhere, and must stop this hideous plan with the help of the X-Men.

When Dr. Ohn's Time Dilation Accelerator falls into the wrong hands, all the criminal minds of the city vie for the portal technology. Peter and Mary Jane are celebrating Felicia Hardy's engagement to Jason Macendale when they overhear plans for a major heist.

The Crime Lords, led by Silvermane, are holding the Kingpin accountable for his failure to eliminate Spider-Man. So six of the wall-crawler's greatest enemies are called together to do the job: Doctor Octopus, Mysterio, the Scorpion, the Rhino, the Shocker and the Chameleon. Unfortunately, Spidey's powers have been on the blink due to the changes in his blood chemistry.

The six supervillains can't believe their eyes when Spider-Man walks into their trap at the warehouse. But it's obvious why, when they easily overcome and unmask the fraud. Meanwhile, Silvermane and the Crime Lords grow more disenchanted with the Kingpin and want to put him out of business. However, Kingpin beats them to the punch, kidnapping Silvermane.

Peter is framed for a crime he didn't commit and it's up to blind lawyer Matt Murdock to prove his innocence, who is also known as the Man Without Fear, Daredevil.

Peter is shocked by Mary Jane's new powers, so they seek Curt Connors' help in figuring everything out. Mary Jane tells them about a dream she's been having, which may be a clue to her disappearance. But Hydro-Man finds them and kidnaps her again.

Norman Osborn hires the Hobgoblin, a hitman and thief, to take out Osborn's "silent" partner Wilson Fisk, the Kingpin. When he fails in the attempt, the Hobgoblin changes sides, kidnapping Norman's son, Harry. Harry just happens to be best friends with Peter Parker.

When Aunt May is slightly injured by one of the Hobgoblin's pumpkin bombs during the kidnapping of Harry, Spider-Man enters the fray with a vengeance. After several battles, the trail leads Peter to Oscorp and Harry's own father. For Peter, rescuing his friend is easy compared to explaining to Harry that his own father is involved.

Wolverine catches up with Spider-Man, hot on the trail of the missing Hank McCoy. Discovering his location and the plot to destroy all mutantkind the two team up and rescue Beast in the nick of time just as he was about to become the first test subject of Landon's horrendous plan. But when Landon accidentally falls victim to his own experiment he is changed into a giant monster that feeds on electrical energy.

Harry Osborn is haunted by dreams of his father, the Green Goblin, and Spider-Man. The Goblin visits him and guides him to the Goblin formula and weapons. Meanwhile, the Punisher promises Anna Watson that he will find Mary Jane, and on top of his list of suspects is Peter Parker.

Spider-Man is transported to an alien world, where he meets the Beyonder, a being who wants to see if good is stronger than evil. He then summons a group of the greatest villains from Earth to this world, telling Spider-Man to put together a group of heroes to fight them and save the planet.

Felicia Hardy, now transformed into the Black Cat, is blackmailed into working for the Kingpin until he can replicate more of the "Super Soldier" serum.

Peter and Mary Jane's big day arrives, but things aren't going to go to plan if Harry Osborn gets his way. With guests including Flash Thompson, Liz, Aunt May, Anna Watson, Felicia Hardy, J. Jonah Jameson, Robbie Robertson and Wilson Fisk, along with gate crashers including the Green Goblin, the Kingpin, Alistair Smythe, the Scorpion, the Black Cat, Herbert Landon, the Mega-Slayer, Norman Osborn, and an army of robot Goblin Warriors, it'll certainly be a day to remember.

Spider-Man summons the Black Cat from Earth, who despite her anger at being kidnapped, decides to help him fight the villains on the alien planet. The heroes must defeat the Red Skull, Doctor Octopus, and Alistair Smythe's robots while protecting a group of rebels, who are trying to take their planet back.

Dr. Doom reverts the Thing to his human form and holds the other heroes prisoner. In an attempt to free his friends, the Thing tells Dr. Doom about the Beyonder. Dr. Doom then steals the Beyonder's powers, but they begin manifesting themselves in the form of creatures from Dr. Doom's dreams.