Season 1: Peter begins attending Horizon High after gaining powers. Norman Osborn establishes the rival Osborn Academy, secretly designing military hardware. Horizon faculty star Otto Octavius suffers an accident fusing mechanical arms to his nervous system, setting off his descent into villainy. The Jackal unleashes a retrovirus triggering the Spider-Island outbreak, infecting Gwen Stacy and mutating citizens, while Miles Morales gains permanent spider abilities. In the finale, Norman frames Harry with Hobgoblin technology, forcing Harry to renounce his father.
Season 2: A dying Doctor Octopus uses the Living Brain to swap consciousness with Peter Parker, becoming the Superior Spider-Man. Otto attempts to prove himself a superior protector, but when confronted by Peter's surviving subconscious and crises involving the Symbiote and Cloak & Dagger, Otto acknowledges Peter's moral superiority and willingly surrenders the body. The season concludes with the four-part Goblin War, in which Norman transforms into the Dark Goblin before being thwarted by the united Spider-Team and Harry.
Season 3: Venom summons an alien symbiote invasion and the dragon-like World Killer to Earth, infecting Max Modell to tear open an interdimensional gateway. Peter unites the Spider-Team with the Avengers and uses scientific resonance frequencies combined with Horizon memories to purge Modell's infection. Though the Horizon High campus is destroyed, Peter uses Stark grants to establish an independent, student-led research institution.