Spider-Man accepts Nick Fury’s offer to become the Ultimate Spider-Man and meets his new allies of young heroes consisting of Nova, White Tiger, Power Man and Iron Fist. Meanwhile, Norman Osborn orders Doctor Octopus to send the Frightful Four to target Spider-Man. Spider-Man ends up having to get help from his new allies to fight off the Frightful Four.

After a childish argument between Spider-Man and Nova gets their entire team grounded, the super-youths go through S.H.I.E.L.D.'s database of the most wanted supervillains to see who they can defeat and apprehend in order to impress Nick Fury. When the choices Batroc the Leaper, Blizzard, Melter, MODOK, Toad, Whirlwind, and Lady Porcupine prove unpopular, Spider-Man and his team go to Latveria to track down Doctor Doom. The young heroes fairly easily capture Doom, but things take a turn for the worst when Doctor Doom tricks the team into taking one of his Doombots aboard the Helicarrier.

Under the supervision of Osborn, Doctor Octavius obtains a sample of Spider-Man's blood in order to create a creature that rivals the powers of the wall crawler. Meanwhile, Peter attempts to balance his friendship with Harry with his time with his SHIELD teammates.

When Spider-Man meets his idol Iron Man, he receives a specialized gift: the Iron Spider suit. However, Spider-Man experiences difficulty learning how to use the suit and begins to neglect his teammates. Meanwhile, the heroes battle the Living Laser, who takes advantage of Spider-Man's lack of experience using the new suit.

Taskmaster goes undercover and infiltrates Peter's school to seek out Spider-Man. Spider-Man and White Tiger must put their differences aside and find a way to defeat an opponent who can mimic all of their physical abilities.

Spider-Man agrees to a video interview with budding news reporter Mary Jane Watson, who gets a more exclusive scoop than she could ever have anticipated when Spider-Man and The Incredible Hulk engage in an all-out battle against Zzzax throughout Manhattan.

It is bad enough Spider-Man catches a cold, but things drop from bad to worse when a new Spider-Man dressed in black attempts to replace him. Are his friends right and is his jealousy is getting the best of him, or is the new Spider-Man Venom's latest victim?

While on a field trip, Spider-Man and his superhero friends encounter the mighty Thor, who is transformed into a frog by his mischievous half-brother Loki. Now, the heroes must venture to the magical world of Asgard in order to save the nine realms from Loki's wrath.

Spider-Man and Wolverine must overcome clashing personalities and styles in order to defeat Mesmero and Sabretooth.