Peter Parker and his college science professor Dr. Curt Conners explore neogenics as a method of limb regeneration. But while experimenting on himself, Connors accidentally becomes the Lizard, a half-man, half-reptile monstrosity that terrorizes Manhattan and subsequently kidnaps his own wife. Spider-Man must stop the Lizard, but his task is doubly difficult because he doesn't want to hurt the good friend he knows is trapped inside.

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 Spider-Man and sends three slayers after him. Spider-Man 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.

Dr. Otto Octavius becomes the mad Dr. Octopus when his robotic arms become fused to him in a laboratory accident. He then seeks revenge for the humiliation the Hardy Foundation has caused him, so he kidnaps Felicia Hardy and holds her ransom.

The Master of Illusion, Mysterio has fooled the city and J. Jonah Jameson into thinking Spider-Man has turned to crime. However, Spider-Man manages to find Mysterio, only to be brought to a trap of special effects.

J. Jonah Jameson hires Dr. Farley Stillwell, a genius in genetic engineering, to make a new superhero that can match and defeat Spider-Man. With a willing participant, Mac Gargain, they engineer the DNA of a scorpion and him together to form a new hero, the Scorpion. However, when Gargain thinks they have turned him into a freak, the hero turns into a monster and goes on a rampage. Spider-Man is forced to step in to stop the creation from killing its creator.

Robbie has set Peter up with a job interview with a researcher by the name of Dr. Mariah Crawford. However, when he gets to her lab, he finds her under attack by a monstrous man who deems himself Kraven the Hunter. Spider-Man leads Crawford away from Kraven to the roofs. There, Crawford tells Spider-Man that Kraven was not always that way, that in fact she loved him as Sergei Kravenoff. Crawford tells of an accident years back that would have killed Sergei had she not used a dangerous potion that saved his life and gave him the strength and instinct of an animal, but turned him mad. Meanwhile, while looking for Crawford at her apartment, Kraven learns of her connection to Robbie and kidnaps him. He then threatens to kill Robbie if Spider-Man does not come to him with Crawford.

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.

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.

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.

An international spy and hitman known as the Chameleon plans to assassinate two major diplomats on the brink of signing the peace proposal of the century. S.H.I.E.L.D. director Nick Fury solicits J. Jonah Jameson's assistance in an effort to prevent the "human shape-shifter" from derailing the proposal signing. But only Spider-Man with his super keen "spider-sense" can discern who is really whom and stop the criminal before it's too late.

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.

Mary Jane is being stalked by her former boyfriend, Morris Bench, who's undergone an accidental metamorphosis and become Hydro-Man. Sweeping Mary Jane off her feet in a wave of water, he insists she will love him. Spider-Man, with the help of Mary Jane, must put a stop to the semi-liquid villain.

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.

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.

Dr. Mariah Crawford has developed a cure for Spider-Man's disease, but she is reluctant to give an untested serum to him that may result in permanent loss of his powers or worse. After an angry outburst from Spider-Man, however, she hands it over. Peter, at the ESU lab, is secretly observed by Michael Morbius, who then swipes the infected blood sample after Peter leaves for the night. Working alone in the campus bell tower with borrowed equipment, Morbius has an accident which will change him forever.

The Punisher comes to New York to deal with the mutating Spider-Man, who has just grown four extra arms, and is in search for also mutated Morbius who is killing innocent people, and the people of New York blame Spider-Man for all that is happening.

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 Spider-Man's heels.

The vampire hunter Blade arrives in New York to destroy Morbius, but Spider-Man wants to revert Morbius back into his human form.

Morbius attempts to use the Neogenic Recombinator to turn everyone else into a vampire. Spider-Man and Blade try to stop him, and Morbius' mutation worsens. Morbius kidnaps Felicia Hardy in order to transform her into a vampire.

Dr. Curt Connors is set to study the Tablet of Time, a recently discovered ancient artifact that is said to restore a person's youth. Dr. Connors believes he can cure Spider-Man's mutagenic transformations with the tablet.

With the Tablet of Time, Silvermane's youth is restored, but he continues to grow younger until he finally becomes an infant.

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.

Spider-Man seeks Curt Connors' aid to help reverse the aging effects of the Vulture's talons. Meanwhile, the Vulture sporadically turns into the man-spider from the mutagenics he absorbed with Spider-Man's youth. At the same time, the Scorpion grabs Dr. Farley Stillwell to seek a cure for his own mutation, while Connors is feeling the onset of his reptilian transformation.

Peter discovers that Mary-Jane is working with a mysterious cult. Baron Mordo, head of the cult, wants them to steal the Wand of Watoom to free his master, Dormammu. When Mordo manages to get his hands on the wand, Spider-Man must team up with Doctor Strange and his sidekick Wong to stop them.

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. However, his biggest fan, a little girl named Tyina, is determined to make Spider-Man change his mind.

Spider-Man loses his memory and becomes partners in crime with Dr. Octopus.

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.

While a gang of jet-pack wearing thieves run by Jackson Weele, an ex-pilot in a rampaging gyro-wheel, plunder the city, Peter tries to deal with his alter-ego giving him competition with Felicia Hardy. Meanwhile, a good kid with a criminal record, Robert Farrell, tries to help his ailing mother by using his science-savvy and the gang's technology to arm himself as the Rocket Racer. While Spider-Man's fighting crime, the mysterious "Jason Phillips" starts to make moves on Felicia.

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.

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.

Worried that the Kingpin is going to eliminate him after the botched framing of Peter Parker, Alistair Smythe arranges a meeting with Spider-Man to give him information about the Kingpin. When Spider-Man arrives, he discovers Smythe has been turned into a spider-slaying cyborg. However, when his programming malfunctions, he goes after the man he feels responsible for his father's death, Norman Osborn. Peter must fight a crazed Smythe, as well as his feelings, after he discovers Mary Jane, the woman he loves, and Harry, his best friend, are engaged.

Robbie Robertson is losing his son, Randy, to a gang of thugs lead by Tombstone. When this harder-than-stone hitman tries to use his history with Robbie to kill a story about his new boss, Alicia Silvermane, he runs afoul of Spider-Man. Both discover Robbie's bond with his child and his ethical resolve is mightier.

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

Ex-employee of Stark Industries, Dr. Jonathan Ohn, invents a portable interdimensional technology that accidentally makes him the living embodiment of a portal. Calling himself the Spot, he tries to steal money to fund his research. But his unstable invention has created a vortex that threatens to engulf New York.

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.

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.

Spider-Man captures a gang of thieves, and it looks like Robbie Robertson is their leader. Peter Parker and J. Jonah Jameson must team up to try to clear Robbie's name. But while Jameson returns to the skills he had as an investigative reporter, Peter must keep him safe from Tombstone.

Doctor Octopus is blackmailing the mother of Felicia Hardy, and she begins to realize that her family has some dark secrets. Some snooping in the Daily Bugle files by Peter, and a confession by Anastasia Hardy, reveal that Felicia's father was really the Cat Burglar, a thief who got rich from the gains of an enormous heist. The Kingpin joins forces with Doc Ock to spring Hardy from jail, as Hardy holds the secret to the 1940s "Super Soldier" formula that created Captain America. To ensure the Cat Burglar's cooperation, the Kingpin kidnaps Felicia.

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.

When a savage creature begins attacking people in New York, the 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.

While settling in to her new role as a hero, the Black Cat is captured by Alistair Smythe, now working for Silvermane, who is trapped in the body of a baby. Smythe delivers Spider-Man an ultimatum: capture the Scorpion or the Vulture within 24 hours, or the Black Cat dies.

Deborah Whitman has located Morbius, the Living Vampire, and brings him back to ESU to work on a cure. Just before leaving town, Felicia Hardy hears of this and uses the trip as an excuse to stay behind as the Black Cat. Together with Spider-Man 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 Spider-Man, the 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.

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.

Mary Jane is back, and she has got the lead role in a major film. But when filming starts, all hell breaks loose, and Mary Jane vanishes from the studio. Spider-Man must fight to ensure that he doesn't lose Mary Jane again, even if it means teaming up with Mysterio. And when it's all over, Peter has a secret to tell.

Peter and Mary Jane get engaged. The happy couple goes to ask Dr. Connors if he'll give away the bride, not knowing that he's been fighting against the return of the Lizard. While they are talking to him, three more humanoid lizards attack and kidnap Dr. Connors. With the Lizard taking over and Spider-Man captured, Margaret Connors, Mary Jane Watson, and Debra Whitman will have to save the day.

Upon returning to his new apartment, Peter is confronted by the Prowler. Revealing himself to be Hobie Brown, he tells Peter that he knows about Peter's connection to Spiderman, and that somehow the Kingpin is involved in all this.

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.

After a visit from an "old friend" of the family, Peter travels to Russia to investigate the mystery of his parents disappearance, and runs into some old friends.

Still in Russia, Peter discovers that searching for clues to his family's past isn't easy when he has to battle the Insidious Six and the Red Skull.

Robbie and Peter encounter an old professor who knows about the Six Forgotten Warriors.

Spider-Man and the Warriors join forces to stop the Kingpin from activating the doomsday device.

Red Skull reveals his Doomsday Weapon, the powerful Electro.

Mary Jane and Peter arrive in Niagara Falls for their postponed honeymoon, but it is soon interrupted when Hydro-Man returns and kidnaps Mary Jane.

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.

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.

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.

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

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.