|Vulture, Electro, Sandman, Rhino, Kraven the Hunter, Mysterio|
|New York City, New York State|
After a planned jailbreak put together by Doctor octopus, the group then went after Spider-Man. The team defeated Spider-Man, but he escaped seeing that old strategies were not going to work.
After a alien symbiote attached itself to Peter Parker's costume, it made him stronger enabling him to defeat the entire Sinister Six with ease, using villains to fight each other.
Second FormingEditIn the episode "Reinforcement," the Master Planner (later to be known as Dr. Octopus) reforms the team with himself and Shocker replaced by Mysterio and Kraven the Hunter.
The team uses an robot substitute for Mysterio and illusion of Vulture to help Rhino and Sandman escape. Meanwhile, Kraven the Hunter helps Electro escape from Ravencroft Institute.
After his escape, Electro and Vulture attack the skating rink near the town's Christmas tree, attracting Spider-Man attention. After taking them out, Sandman and Rhino attack. After luring him to a nearby pier, Spider-Man defeats Sandman with water from a fire hydrant and froze up due to the cold weather. Spider-Man then tricked Rhino into falling into the frozen water. Then, Mysterio and Kraven attack Spider-Man using illusions of Dr. Octopus and Shocker.
After hitting Kraven's face with a perfume bottle, Spider-Man is attacked by Mysterio. Kraven accidentally gives away Mysterio's robot duplicate, which was about to explode. Spider-Man then saves a mall Santa Claus and Elf as Kraven is knocked out by the robot explosion. After webbing up Kraven, and making sure it's the real Mysterio, Spider-Man attempts to interrogate Mysterio to find out who the Master Planner really is. As the real Mysterio is arrested, the Tinkerer helps the rest of the team to escape.
- Greg Weisman said that there was going be a different line-up of Sinister Six every season.
- Although the group appeared in Spider-Man, this is the first time their comic book name is used. It is also the first time that Doctor Octopus formed the group, as he originally did in the comics, rather than Kingpin.