Spider-Man's dream of joining the Avengers becomes a nightmare when Loki switches bodies with the web-slinger, turning his new teammates against him. Spider-Man and his friends team up with the Avengers to stop Loki and Doctor Octopus from destroying New York City with an army of Venomized monsters.

While trying to become a crime fighter, Flash Thompson gets permanently bonded with Venom. It's up to Spider-Man to rescue his one-time school bully from the attentions of Venom, Beetle and Taskmaster. In the end, Nick Fury decides to give Spider-Man his list of teenaged superheroes.

Spider-Man wants to recruit Cloak and Dagger as new warriors for his S.H.I.E.L.D. team. Complicating the matter, however, are Dormammu taking control of Cloak and Dr. Strange in an attempt to invade Earth, and Cloak and Dagger's own trust issues.

Science genius Amadeus Cho proves perfect to operate the Iron Spider armor. The only trouble is he's Peter Parker's class rival.

A mysterious thief known as The Vulture has been causing trouble. Spider-Man decides to track him down, and discovers he's a young man who has trouble remembering his past.

Spider-Man accompanies Wolverine to the Savage Land to recruit Ka-Zar and his pet smilodon Zabu. During this time, they discover a plot by Taskmaster and Kraven the Hunter to abduct Zabu as part of Kraven the Hunter's ritual that would render him immortal.

The cast of "Jessie" gets animated in this special crossover episode that finds the Manhattan nanny in possession of a medieval sword coveted by the infamous Morgan Le Fey. Jessie and Spider-Man team up to save Halloween and the world from Le Fay's evil plans.

Now that the other young heroes have been assembled, Spider-Man must lead them into defending the Tri-Carrier from the Thunderbolts (consisting of Taskmaster, Vulture, and Cloak and Dagger) where they managed to spring Green Goblin, Doctor Octopus, Beetle, and Scorpion from their cells.

Spider-Man sees what the world would be like without him when Nightmare takes the web-slinger on a journey through his past, present, and future.

Spider-Man learns that the Green Goblin is planning to travel across the Multiverse using the Siege Perilous he stole from S.H.I.E.L.D. and the energy of Electro to collect the DNA of other Spider-Men. Spider-Man follows his enemy to the futuristic world of Marvel 2099 (which is drawn in CGI) and helps boost the confidence of Spider-Man 2099. Then he travels to a gender-swapped universe and teams up with Spider-Girl to defeat their world's versions of the Green Goblin.

While chasing Green Goblin across the Multiverse, Spider-Man arrives in the Marvel Noir universe where he helps Spider-Man Noir renew his friendship with Marry Jane. Then Spider-Man heads to a cartoonish world inhabited by anthropomorphic animals where he helps Peter Porker find the will to be Spider-Ham again.

As Spider-Man continues chasing Green Goblin across the Multiverse, he lands in a medieval-based world where he helps Spyder-Knight take down the Alchemist (the medieval version of Doctor Octopus) and his Kraken creation to save York. Then, his last stop before heading back home is an alternate version of the Ultimate Universe where he helps Miles Morales overcome the guilt of being unable to save his world's Peter Parker from death and fight the Ultimate Green Goblin.

After Spider-Man finally ends up back in his own universe, he finds Green Goblin has injected himself with the Spider-Men DNA from all the universes to become the Spider-Goblin. With Electro's help from the Siege Perilous, he summons all the Spider-Men dubbed Web-Warriors to battle the Spider-Goblin and save New York even when Electro plans to destroy it.

The S.H.I.E.L.D. Academy has been opened up at the Triskelion by Nick Fury as Spider-Man's group gets their education from Mr. Frank and guest instructors like Captain America and Hawkeye. Halfway into their education, Spider-Man and Iron Spider unknowingly reactivate an old World War II villain named Arnim Zola.

When Rhino learns that his archenemy Flash has become a hero, he starts a bitter rampage through New York. Spider-Man and Agent Venom are the last line of defense with help from Hulk. However, Hulk and Rhino face in battle and only Spider-Man and Agent Venom should stop now so to not cause destruction.

Nick Fury has been infected by nanite versions of Doctor Octopus' Octo-Bots. While the others face off against Doctor Octopus, Spider-Man and Power Man work with Ant-Man to enter Nick Fury's body and get the Octo-Bots out of him.

Craving Mexican food following an entire day training with Hawkeye, Spider-Man, Power Man, and Squirrel Girl sneak out of the Triskelion after hours for late-night burritos. Along the way, they must contend with Mesmero's plot to use the cellular network to brainwash everyone like he did with Batroc the Leaper, Boomerang, Grizzly, and Shocker.

Following Spider-Man's fight with Molten Man, the Inhumans have declared war on Manhattan as Nick Fury blames the exchange student Triton. Spider-Man and Triton discover that Maximus has brainwashed the rest of the Inhuman Royal Family (consisting of Black Bolt, Medusa, Gorgon, Lockjaw and Karnak) and plans to crash Attilan into Manhattan.

Arnim Zola resurfaces and starts replacing Spider-Man's fellow students with synthezoid versions of themselves.

With most of his fellow students replaced with synthezoids, Spider-Man must work with Agent Venom and Rhino to rescue their classmates and defeat Arnim Zola.

The Collector and the Grandmaster capture Spider-Man, along with every hero, villain and citizen of New York to play a game that will decide the fate of the entire planet.

The Collector and the Grandmaster's game continues as Spider-Man teams up with members from the Avengers and the Agents of S.M.A.S.H. to play for the fate of the planet.

Spider-Man has to change the rules of The Grandmaster's game to save the citizens of New York and prevent the villains from taking over Earth.

Spider-Man fights side-by-side with The Collector in an attempt to free all of Earth's heroes and villains from the Grandmaster and set everything right again.