One year after becoming Spider-Man, a teenage Peter Parker is approached by Nick Fury to train with S.H.I.E.L.D. Spidey turns Fury down, but soon finds that villainous forces may require him to join the big leagues after all.
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.
Spider-Man meets his idol, Iron Man, who has a gift for the web-slinger - an iron spider suit. While Spidey tries to master this new piece of armor,the relationship the web-sligner has with his allies is put on the line by the one he is developing with the armored avenger.
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 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.
After defeating Mesmero, Spider-Man and Wolverine magically switch bodies and if that isn't strange enough, they must team up to defeat Sabretooth.
Venom resurfaces using Harry as his host yet again; 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.
After a fight with Whirlwind, Spider-Man insists on a weekend off from Nick Fury and S.H.I.E.L.D.. Unfortunately, Doctor Octopus chooses this very time to attack Spider-Man when his job is threatened by 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 and Luke attempt to finish their science projects but get get side tracked by Juggernaut.
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.
Finding Hulk is an alien probe, Spider-Man protects him from SHIELD by taking him home. He thinks he's home free until Aunt May comes home early from a trip.
While trying to hide Hulk from his Aunt, Peter must also try to prevent an alien invasion.
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.
After sparring with the legendary Captain America, the team loses Cap's shield which naturally lands in the hands of Doctor Doom.
When an unexpected date between Phil Colson & May Parker gets interrupted by the Beetle, Spider-Man must put aside is uneasiness about them dating and defeat the threat at hand.
Octavius turns on Osborn by injecting him with the mutated DNA of Spider-Man which transforms him into a monster which a guilt-ridden Spider-Man insists upon taking on alone.
Spider-Man, his team and S.H.I.E.L.D. attempt to protect Harry Osborn from the Green Goblin and the truth about his father, but when Venom emerges it's suddenly twice the trouble for the team.