Adrian Toomes has just been fired from his job at Oscorp, owned by Norman Osborne. Angered at this, Toomes decides to get revenge on Norman and becomes the Vulture, creating a special flight suit that allows him to fly. As if the Vulture wasn't already a handful for Spidey, a mysterious figure who has been watching Spider-man closely, dispatches a group called the Enforcers to test his skills.
An electrician named Max Dillon becomes the supervillain known as Electro after a freak accident and it's up to the Spectacular Spider-Man to stop his rampage. Meanwhile, Peter tries to tutor the popular Liz Allan.
Dr. Connors gives himself the mutated lizard DNA serum, unaware that it was electrified by Electro in a prior lab battle. The result: a transformation that turns him into a savage humanoid lizard.
Spider-Man finds himself up against a new villain-for-hire: the Shocker.
Criminal thug Flint Marko volunteers for an experimental process sponsored by the Big Man and Norman Osborn, and is transformed into... the Sandman! Meanwhile Peter helps his friend, Harry Osborn, join the football team.
Having failed with the Sandman, the Big Man and Norman Osborn perform a transformation on Marko's partner Alex O'Hirn, turning him into... the Rhino!
Peter takes his date, next door neighbor Mary Jane Watson, to the prom, where the glamorous redhead makes her mark on the student body elite. However, when the new glider-riding threat known as the Green Goblin attacks a black-tie party attended by J. Jonah Jameson and his son John, Peter is forced to abandon his date and risk his life against the villain as Spider-Man.
The Green Goblin breaks into Norman Osborn's secret experimental lab and sabotages Dr. Octavius' experiments, causing the scientist's manipulator arms to merge to his body and creating a new villain: Dr. Octopus!
When Peter goes to a Halloween event, Green Goblin shows up and creates chaos, while Colonel John Jameson prepares to crash land his damaged space shuttle. It's up to Spider-Man to save the day from both catastrophes.
Spider-Man inadvertently comes into contact with the black symbiote creature brought back from space, and it merges with him and gives him a new black costume and new powers... but at a cost.
The newly formed Sinister Six comprised of Doctor Octopus, Electro, Shocker, Vulture, Rhino, and Sandman, face of Spider-man with his new symbiotic black. Also, Mary Jane is taken out for a ride with one of Peter's friends.
When Peter Parker finally realizes that the Symbiote has not only attached itself to his Spider-man costume, but his life and mind as well, Peter has to get rid of it as soon as possible. But the Symbiote realizes this and prepares to defend it self. A battle of wills inside Peter's head is insured. The Symbiote shows Peter his own past and how Peter later became Spider-man.
As Thanksgiving arrives, Peter has to deal with Aunt May's release from the hospital and an attack by a new enemy: the alien symbiote merged with Eddie Brock, forming a new identity: Venom!
In the Season 2 premiere, Spider-Man faces a new enemy named Mysterio. Meanwhile, Peter continues his search for Eddie.
Spider-Man faces off against Kraven the Hunter while Peter must decide between Liz Allen and Gwen Stacy.
Mysterio and Kraven join the ranks of the Sinister Six (including Sandman, Rhino, Vulture and Electro) in an attempt to capture Spider-Man once and for all.
While on a tour of a condemned building that is about to be demolished with his mentor Norman Osbourne, Peter finds out that the detonators they used were sabotaged to blew up earlier then previously thought. Later, while inside a mall with her friends, Gwen gets kidnapped by one of Master Planner's henchmen, Electro; in an attempt to course her father, Captain George Stacy, into helping him out.