Summer is over for Peter Parker and school's ready to start - both literally and in the real world of crime-fighting - as Spider-Man faces his first real challenge, the Enforcers, and his first real super-villain, Vulture.
Peter Parker attempts to tutor the popular Liz Allan while Spider-Man tries to stop Electro, who will stop at nothing to find a cure for the accident that made him who he is.
While Peter takes on the responsibility of helping Aunt May pay the bills while Montana, one of the Big Man's Enforcers, becomes the stunning Shocker to fulfill his responsibility: Eliminating Spider-Man.
Flint Marko is transformed into the invincible Sandman. Meanwhile, Peter risks compromising his cover and break Harry's heart by taking part in the school's American football try-outs. Gwen hopes Peter will take her to the formal dance.
Peter Parker and Mary Jane Watson go to the Midtown High Fall Formal. Meanwhile, the mysterious Green Goblin tries to force L. Thompson Lincoln to step down as NYC's Big Man of crime. Will Spider-Man be able to take on this new threat?
Peter and Spider-Man learn that their actions have consequences when Otto Octavius becomes the supervillain Doctor Octopus following a lab accident caused by the Green Goblin.
With Electro's help, Doctor Octopus breaks himself, Vulture, Shocker, Sandman, and Rhino out of prison to quench their mutual revenge on Spider-Man. Even with his new black suit, Spidey finds his old enemies are more than he can handle.
Spider-Man encounters master thief Black Cat and bonds with an alien symbiote, granting him enhanced abilities. Meanwhile, the Chameleon impersonates Spider-Man, forcing the real Spider-Man to join forces with Black Cat to stop him.
While Colonel John Jameson struggles to land his damaged space shuttle, Spider-Man struggles to defeat the Green Goblin, who also threatens Hammerhead and Tombstone.
With May hospitalized and his friendship with Eddie ruined, Peter gains enough self-awareness to realize the symbiote is affecting his personality. The struggle between Peter and the symbiote evolves into a war within Peter's own mind.
As May is released from the hospital, Eddie, now transformed into the vicious Venom after bonding with the symbiote, seeks revenge on Peter by targeting his loved ones, including May and Gwen, drawing Spider-Man into motion to defeat him.
While Peter struggles to find the proper opportunity to talk to Gwen about their first kiss, Spider-Man must face a new supervillain, the self-proclaimed sorcerer Mysterio.
While Peter is conflicted over his choice to be with either Gwen or Liz, Kraven the Hunter comes to New York. After being defeated easily, Kraven enlists Professor Miles Warren to help transforming him into the "ultimate hunter".
Near Christmas Day, the Master Planner reconstitutes the Sinister Six with Vulture, Electro, Sandman, Rhino and new members Mysterio and Kraven. Meanwhile, Peter finds his wandering eye prevents him from being with Gwen.
On New Year's Eve, the Master Planner and the new Sinister Six kidnap Gwen to coerce her father, police captain George Stacy, into giving them high level clearance, allowing the Planner to effectively run the world.
While Peter gets invited to his rival Flash's birthday party, Spider-Man must face the Sandman once again, who is attempting to rob an oil tanker. Peter also witnesses Harry's return from Europe and begins to fear of Venom returning.
Eddie, re-bonded with the symbiote, frames Spider-Man for a crime spree. Meanwhile, spores from the alien symbiote infect John Jameson. J. Jonah encourages his son to become a superhero, but John comes to see Spider-Man as a menace.
Peter's identity as Spider-Man has been outed by Venom, leaving Peter and his loved ones vulnerable to his enemies. Spider-Man has his final battle with Venom, where he must find a way to separate Eddie and the symbiote once and for all.
A gang war looms as Silver Sable, Hammerhead, and Doc Ock vie for a prize that could change the balance of power in New York. Spider-Man finds himself in the thick of this fray and must rely on the unexpected help of Rhino to defeat them.
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