As Peter Parker joins the school for geniuses, Horizon High, his best friend Harry Osborn gets suspended after Spencer Smythe claims that he sabotaged a Vibranium machine. In his first adventure as a superhero, Spider-Man goes up against the Vulture.
Spider-Man faces off against the Scorpion as he attempts to rob the science museum. Spencer secretly creates a giant robot that steals some of Harry's devices.
As Norman Osborn creates the Osborn Academy for Geniuses, Peter takes a tour there. Harry becomes suspicious of Spider-Man, while Jackal is plotting a robbery.
As Spider-Man is having a hard time juggling his many tasks as a regular kid while being a superhero, he has to stop Black Cat from stealing the V-252 symbiote.
After Harry's innocence is proven, Max holds a dance to celebrate the news. As Raymond tries to join the Oscorp Academy, Aleksei Sytsevich turns into Rhino following an accident.
After an encounter with Sandman, Spider-Man finds out that he's only trying to reunite with his daughter Keemia. As he sets out to help him face the evil Hammerhead who was behind turning him into Sandman.
As the V-252 bonds with Spider-Man, he discovers a dark side to the symbiote. Vulture joins forces with Norman to get their hands on the V-252.
As Spider-Man tries to prove to Max the truth about the V-252, Ghost crashes the Stark Expo in order to take control of the place Spider-Man is forced to use the V-252 to be able to stop Ghost.
After getting bitten by an experimental spider, Miles Morales gains superpowers. Now it's up to Peter to teach him how to control his newfound powers. Spencer teams up with Alistair as they attack Miles' neighborhood with giant Spider-Slayers.
Spider-Man and Miles find themselves being used by Kraven the Hunter to be part of his TV show, as Norman hires Kraven to bring him the two Spider-Men for experimentation.
Spider-Man joins forces with the Hulk to stop a gamma-powered Man-Wolf from turning the people of Manhattan into werewolves on Halloween.
When Hammerhead's minion Randy Macklin steals Harry's cryogenic gauntlet, he turns himself into Blizzard. Spider-Man has to find a way to stop Blizzard from wreaking havoc on the city.
When the V-252 breaks out of the Avengers Mansion, it finds its way to Flash while he's playing a football game at Midtown High. Spider-Man sets out to stop the symbiote from causing damage.
After Screwball pulls out a prank during the opening at a power plant, Spider-Man has to foil Absorbing Man's evil plans and save Screwball and Randy Robertson.
After a battle with Crimson Dynamo causes Otto Octavius' robot arms to fuse to his body, Spider-Man wants to use his newfound skills to help him capture Dynamo.
As Octavius joins Spidey and Miles to keep the city safe, they realize that Octavius has other plans in mind. Spider-Man faces a new enemy in the form of Oscorp scientist Dr. Curt Connors who turns into Lizard.
As Peter sets out to prove to Harry that his father is plotting to eliminate Spider-Man, things take a turn when Jackal attacks the Osborn Academy to turn the students into Rhinos.
Peter joins forces with Gwen and Harry to find the whereabouts of the missing Raymond. Their search leads them to discover a plot to make an army of Jackal clones with spider powers.
When Peter's experimental stealth suit is stolen by an unknown villain, Spider-Man receives help from unlikely allies to stop the villain from executing a destructive plan.
As everyone in the city gets infected with the spider virus, Spider-Gwen and Spider-Man help Black Widow find Crossbones and his Hydra team before they rob the Vibranium storage vault.
After Gwen mutates into a spider monster, Peter sets out to cure her, while Kraven the Hunter makes things worse by wreaking havoc on the city as part of his TV show.
As more people turn into Spider-Monsters, Peter and Harry must find a way to stop Norman Osborn who appears to be behind this crisis. But they're in for a surprise when they find out the identity of the real mastermind.
After the Jackal captures both Spider-Man and Miles, they make a desperate attempt as they join forces with Anya and Harry to defeat the Jackal and save the city.
After Norman gives Harry the Hobgoblin armor, Spider-Man has to face a grave threat, as he must battle the "Sinister Five" who plot to brainwash him so that he joins them in their spree of destruction.
After Doctor Octopus attacks Horizon High, Spider-Man stops him but he's suddenly attacked by Hobgoblin who is determined to do whatever it takes to get rid of Spider-Man. Harry is left to make a fateful decision.