As the series begins, Peter Parker has been Spider-Man for one year. He has saved lives and fought supervillains, but he is still in the process of learning how to be a superhero. Nick Fury of S.H.I.E.L.D. offers Peter the chance to train to be a real superhero and become "The Ultimate Spider-Man". However, beforehand Peter will have to learn how to work with a team of four fellow teenage superheroes.The teen heroes Spider-Man will be teaming up with are Nova, White Tiger, Iron Fist, and Power Man.
Spider-Man accepts Nick Fury's offer to become the Ultimate Spider-Man and meets his team of teenage allies, 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, who ends up needing help from his new allies to fight off the villains.
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.
Doctor Octopus' newest creation Venom, an unstable clone derived from a bloodsample from Spider-Man, shows up at Harry Osborn's house party and attacks Spider-Man and the other trainees, jumping from host to host.
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 IncredibleHulk engage in an all-out battle against Zzzax throughout Manhattan.
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.
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.
Hulk smashes back into Spider-Man’s life when he falls sick with an alien infection caused by the Phalanx. Fearing that S.H.I.E.L.D. will want to lock the Hulk away rather than help him, Spider-Man sees no choice but to take Hulk home and keep him hidden from Aunt May, the Phalanx and Fury.