Året efter, han blev Spider-Man, bliver teenageren Peter Parker kontaktet af Nick Fury, som vil have ham til at træne med S.H.I.E.L.D. 'Spidey' takker nej men finder snart ud af, at onde kræfter tvinger ham til at være med blandt de bedste alligevel.

Spider-Man accepterer Nick Furys tilbud om at blive den ultimative Spider-Man og møder sine nye allierede, de unge superhelte Nova, White Tiger, Power Man og Iron Fist. Imens beordrer Norman Osborn Doctor Optopus til at sende the Frightful Four efter Spider-Man. Spider-Man bliver nødt til at have hjælp fra sine nye allierede for at bekæmpe 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.

Taskmaster går undercover og infiltrerer Peters skole for at finde Spider-Man. Spider-Man og White Tiger må lægge deres uoverensstemmelser til side og finde en måde at besejre deres modstander, som kan immitere alle deres fysiske egenskaber.

Spider-Man går med til et videointerview med rapporteren Mary Jane Watson, som får et mere eksklusivt scoop, end hun nogensinde havde regnet med, da Spider-Man og the Incredible Hulk sammen går i krig mod Zzzax igennem hele 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.

Venom resurfaces, using Harry as his host, yet again, and this time Harry's neglecting father becomes his main target. While Norman Osborn does not want his potential secret weapon damaged, Spider-Man is confronted with the dilemma of either trying to help Harry on his own or putting his trust in his teammates, who have orders from Fury to finish Venom off.

Efter en kamp mod Whirlwind insisterer Spider-Man på en friweekend fra Nick Fury og S.H.I.E.L.D. Uheldigvis vælger Doctor Octopus samme tidspunkt til at angribe Spider-Man, da hans job bliver truet at Norman Osborn.

When New York is plunged into a mystical sleep, Iron Fist and Spider-Man (who is at first highly sceptical of magic) seek the help of Doctor Strange. In order to break the spell, the three heroes must face their own worst fears in the face of the spell's initiator, the extradimensional entity known as Nightmare.

Peter Parker scrambles to focus his attention between completing his science fair project with Luke Cage and combatting Juggernaut. In his desperation concerning the first case, he decides to "borrow" one of Dr. Connor's inventions ... which (literally) becomes an even bigger threat to the city.

After being late for training, Spider-Man is faced against an evil super army called Zodiac and their leader, Scorpio, who took over the S.H.I.E.L.D. Helicarrier and set it on self-destruct. Spider-Man and Fury must put their differences aside and fight the new menace as a team.

Spider-Man and his team are put on S.H.I.E.L.D. security detail to protect the all-too-critical-for-his-own-health J. Jonah Jameson from the Beetle, a prospect Spider-Man does not enjoy. Things do get personal when Spider-Man must also protect a highly determined Mary Jane, who is on her way to the Bugle for a job interview, from the high-tech villain.

When Phil Coulson wants the heroes to report to the S.H.I.E.L.D. ice base for winter survival training, Spider-Man and his team sneak off for a vacation on a deserted tropical island that Nova finds under "classy." However, they soon realize something is not right with the island and the Sandman will make sure they never leave.

When Spider-Man and his fellow teenage super heroes cause too much damage in a super villain fight, Nick Fury assigns them to work with the super clean-up company Damage Control. While working with Damage Control, Spider-Man uncovers a villainous mystery.

Hulk smashes back into Spider-Man’s life where he is sick with an alien infection caused by the Phalanx. Spider-Man has no choice but to take Hulk home and keep him hidden from Aunt May while protecting him from the Phalanx.

Loki exacts revenge on Spider-Man by turning him into a pig, just in time for the Asgardian Boar Hunt across New York City. Now, Thor, who knows all too well how it feels to be transformed into a helpless animal, must help Spider-Ham survive.

Flash Thompson stars as Spider-Man in a Midtown High musical production, and gets a taste of what Spider-Man's life is really like when the Trapster mistakes the football jock for the real web-slinger.

When Doctor Octopus takes over Iron Man's armors, Spider-Man and team work to stop his attacks on Oscorp and S.H.I.E.L.D.

Spider-Man loses Captain America's shield and must retrieve it from Doctor Doom.

Aunt May goes on a date with Phil Coulson, Peter's principal and S.H.I.E.L.D. supervisor, and the Beetle returns to continue his evil deeds.

The Green Goblin is created.

Spider-Man tries to protect Harry Osborn from the Green Goblin and Venom.