Norman Osborn hires Spencer Smythe to design a machine capable of destroying Spider-Man - the Black Widow Spider Slayer. But when Flash Thompson puts on a Spider-Man costume as a party gag, the deadly machine spots him, and he's carried off in Peter's place.

With Spencer Smythe dead, his son Alistair turns to the Kingpin to help seek his revenge on Spider-Man and others he deems responsible for his father's death. He captures, Eddie Brock, J. Jonah Jameson, Norman Osborn, and Flash Thompson. He then turns his sights on Spidey and sends three slayers after him. Spidey only manages to hold his ground while fighting them individually. However, he is not so lucky when they combine into a super slayer and carry him off to Smythe.

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.

Norman Osborn hires hitman and thief, the Hobgoblin, 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.

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.

After Spider-Man mutates into the Man-Spider, Dr. Mariah Crawford summons Sergi Kravenoff, better known as Kraven The Hunter, to help her track down Spider-Man and cure him of his mutation with a newly developed antidote. Unfortunately, the Punisher is hot on Spidey's heels. Will the Punisher succeed in destroying Spider-Man in his new mutated form or will Kraven and Dr. Crawford reach him first?

Adrian Toomes wants revenge when Norman Osborn attempts to take over his company, Toomes Aeronautical. He becomes the Vulture and immediately kidnaps Norman's son, Harry. Will Spidey be able to rescue Harry from the Vulture's youth stealing talons?

Tired of Jameson giving Spider-Man the rap for all the crime in New York, Peter decides to give up the superhero business once and for all, until he meets his biggest fan, a little girl named Tyina. Can she get Spidey to change his mind?

Peter Parker and Mary Jane are finally a couple, but there happiness is short-lived as the Green Goblin, armed with a time distorter and the true identity of Spider-Man, seeks to destroy Spidey, by any means necessary.

When a savage creature begins attacking people in New York, Black Cat tries to convince Spider-Man that he needs her help to stop it. All clues point to the creature being Kraven The Hunter, but sleuthing by Debra Whitman, Flash Thompson, and the Black Cat solves the case. The beast, Calypso, is related to Kraven, but the Hunter wants to capture and cure her.

Deborah Whitman has located Morbius, the Living Vampire, and brings him back to ESU to work on a cure. Just before leaving town, Felicia hears of this and uses the trip as an excuse to stay behind as the Black Cat. Together with Spidey and Whistler, she has to take on Herbert Landon and the Shocker in order to save Morbius from himself.

There's a new Vampire in town, but Morbius is getting all the blame. Just as Spidey, Black Cat, Whistler and Morbius have the Vampire Queen trapped, Blade bursts in and prevents her destruction. His revelation sets the others against him, while the queen attempts to create an army of vampires. Meanwhile, Harry Osborn discovers Peter's spare Spider-Man mask!

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