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 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.

Spider-Man spends a day in Deadpool's madcap world.

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

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.

When Doc Ock learns that the key to a device that will retrieve Hydra Island is at Aunt May's house, Spider-Man must fight to protect his family.

Spider-Man and Nova team up with The Guardians of the Galaxy on a deep-space adventure to save Earth from destruction.

The Green Goblin is created.

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

Doc Ock launches a surprise attack on Spider-Man and the heroes. They soon find themselves in one of the most challenging battles of the season when they're up against the newly reformed Sinister Six. Norman Osborn also returns as Iron Patriot despite Ock's alternate plans for him.

The Guardians of the Galaxy land on Earth to repair their ship at the same time ex-Nova Corps member Titus leads the Chitauri into targeting Nova's helmet. Now Spider-Man and Nova must work with the Guardians of the Galaxy to defeat Titus and the Chitauri.

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.

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 faces the culmination of all Doc Ock's evil machinations when the new Sinister Six assaults the Web Warriors and S.H.I.E.L.D. Academy at the Triskelion.

Spider-Man and Kid Arachnid travel to alternate dimensions to gather the shards from the broken Siege Perilous.

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?

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.

Spider-Man travels to the mystical city of K’un L’un to help Iron Fist fulfill his destiny. But The Scorpion plans to destroy them both.

Spider-Man must work with his nemesis, Doctor Octopus, when The Green Goblin unleashes Venom on the Tricarrier.

Spider-Man teams up with The Avengers' Captain America and the X-Men's Wolverine to stop a new threat to S.H.I.E.L.D.

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.

Spider-Man and Kid Arachnid arrive in the Noir Universe where they have to prevent Mr. Negative from using the Siege Perilous to drain all the life and color out of the world.