Original Sinister Six
After suffering three defeats in a row from the wall crawling, web-slinging superhero Spider-Man, Dr. Octopus realized he required assistance from others in order to defeat Spider-Man. He got in touch with every known super-villain Spider-Man had crossed paths with and only five responded: the airborne assassin the Vulture, the electrifying Electro, the wild Kraven the Hunter, the mysterious master of illusions Mysterio and the shape-shifting Sandman. Knowing he'd never be able to keep the team together for long, Doctor Octopus quickly formulated a battle plan that would give each of the villains personal glory and Spider-Man an early death. Each individual member of the Sinister Six would battle Spider-Man in a carefully chosen location, until the point where the wall-crawler was no more.
Spider-Man himself had his own problems, as he had somehow lost his powers and prepared to return to normal life as a teenager. While blaming himself for the death of his uncle Ben Parker, Spidey lost his balance and fell down the side of a building, landing and clinging to a flagpole. As Peter returned to his normal life as a student and a freelance photographer, he was unaware of the fact that the Sinister Six realized the Daily Bugle secretary Betty Brant played a large role in Spider-Man's life and kidnapped her, along with an innocent bystander - Peter's aunt May Parker.
It was then left to the Vulture to spill the beans to J. Jonah Jameson, warning him to inform Spider-Man that Betty was being held hostage along with Aunt May and if he wanted to see them alive, he'd have to battle the Sinister Six.
Despite not having his powers, Peter put on his Spider-Man costume and went to fight Electro at an electrical plant. During the battle, Peter somehow regained his superpowers (It was speculated to be a psychological block, caused by his own self-loathing for the loss of his uncle, which he got over when facing a life-or-death situation) and easily defeated Electro. Spidey then battled against Kraven the Hunter- who confronted him with some wild cats- and defeated this foe too. After defeating Mysterio (who utilized robotic duplicates of the original X-Men), the Sandman (who trapped the wall-crawler and himself in an indestructible, airless chamber), and the Vulture, Spidey went up against Doc Ock, who lured him into an enormous fishbowl. The two foes battled and Spider-Man was victorious. All six super-villains were subsequently sent to prison. 
Return of the Six
Many years later, the villains all escaped prison and went to get revenge on the wall-crawler. However, times had changed as Kraven had committed suicide, so the Hobgoblin took his place. The group was organized once again by Dr. Octopus, who claimed they would try to defeat Spider-Man. However, this was a trick, part of a larger plan by which Octavius alone would be the master of the world. The Sandman, at this point in his career reformed, aided Spider-Man in defeating the Sinister Six, ultimately stopping Octavius's plans to conquer the world. 
A few months later, the group reunited once more in a bid to take over the world using alien weaponry. Sandman's foster family was hit with a bomb, and Sandman, believing Octopus had attacked them as punishment for betraying him, joined the other members of the Sinister Six in a plan to take revenge upon Octopus. Despite his grief, however, Sandman contacted Spider-Man and asked him to shadow the group as insurance against him being double-crossed or unexpected surprises.
By this point, Octopus had already obtained his lost Adamantium arms (by killing a wealthy, unethical individual who offered to sell the arms to him) and stealing the old man's robot soldiers and weapons. Octopus easily defeated the other members of the Six with them, then zapped Sandman with a weapon that transformed his living sand body into solid glass (Octopus, however, was apparently not responsible for the bombing of Sandman's foster family, which was apparently done by the other members of the Six in order to coerce Sandman into joining their revenge scheme; in addition, Octopus had not only anticipated the Six's plan to reassemble and take revenge upon him, but had deliberately facilitated it, even secretly paying Electro to help ensure the Six reassembled so that he could coerce the other members into aiding his scheme).
The assembled Sinister Six went off on a rampage, stealing advanced weapons and technology from several sources, including raiding an alien dimension for advanced weaponry and attacking a facility specializing in cybernetics, in the process having several successful encounters beating Spider-Man, the Hulk (in his Professor identity), Deathlok, Solo, and others (before acquiring more advanced alien weapons, the Hulk trounced the other members of the Six, then got stomped upon by Octopus because Octavius had the Adamantium arms).
Merely defeated in his initial encounter with the Six, Spider-Man was left with hairline fractures on one arm and leg, but was able to pursue them with medical attention including cybernetic casts. Eventually, Spider-Man and several other heroes confronted the villains as they were seizing a Hydra base to gain access to deadly, world-devastating weapons (during the Six's raiding assaults on various locations, the group engaged in wanton mass murder, simply exterminating anyone who got in their way, shocking Spider-Man, as, despite their lack of scruples, these particular villains didn't generally kill wantonly). The last member of Octavius's Sinister Six was revealed to be Gog, and a combat between members of the super hero community summoned by Spidey (including the Fantastic Four, Nova, the Hulk, and Solo) broke out, ending when the broken-glass body of the Sandman shredded Doctor Octopus, nearly killing him. 
A variation known as the Sinister Seven was formed by Hobgoblin to fight Kaine, a defective clone of Spider-Man that was killing villains, including Doctor Octopus and the Grim Hunter (Kraven's son). The remaining members of the Sinister Six (Mysterio, Electro, Mysterio, Vulture) first gathered in the aftermath of Octavius's demise. They soon reassembled with Shocker, Beetle, and Scorpia to actively hunt down Kaine. In the meantime, however, Kaine was hunting them. Peter Parker (in the Scarlet Spider costume) was forced to intervene and prevent any of his enemies from eliminating each other.
Venom and the Six
Doctor Octopus was resurrected in time, and remained on bad terms with his former lackeys. Eventually Sandman put together another version for the sole purpose of destroying Doctor Octopus and his ally, Senator Stewart Ward. When Spider-Man intervened, they were forced to add an extra member to their roster as a replacement for Doc Ock: the enraged Venom. The Sinister Six were defeated again (Ironically, Venom subsequently went on to attack the various members of the Sinister Six, nearly killing the Sandman and badly injuring Electro and Kraven before he and his symbiote were briefly separated from each other). 
A few years later, Norman Osborn, the Green Goblin, had been unmasked to the public and imprisoned after losing a battle to Spider-Man. Defeated but unbowed, Osborn concocted a fiendish contingency plan. He contacted a group of super-villains who also bore grudges against Spider-Man, and all of them had been financed by Osborn's fortunes for years. Eager for revenge, the villains agreed to band together, and the Sinister Twelve was formed.
The Sinister Twelve was the largest gathering of Spider-Man's enemies of all time. The major villains not part of the Twelve were either deceased (Mysterio, Kraven the Hunter), retired (Molten Man, Hobgoblin), or incarcerated (the Rhino and Doctor Octopus.)
Mac Gargan, the Scorpion, was the de facto leader of the Twelve while Osborn was in prison, and it was he who kidnapped Peter Parker's Aunt May and threatened to kill her if Spider-Man did not help Osborn escape from jail. A desperate Spider-Man, with help from the Black Cat, broke Osborn out, only to be confronted with the Vulture, Sandman, Electro, Chameleon, Lizard, Hydro-Man, the Shocker, Hammerhead, Boomerang, and Tombstone. Osborn, now in the guise of the Green Goblin, introduced them as the Sinister Twelve. The final member of the group, Scorpion, shocked everybody present when he arrived, revealing that he had bonded with Eddie Brock's alien symbiote, becoming the new Venom. Although Osborn was displeased with Gargan's new power, he nevertheless watched with glee as the assembled villains converged on the hopelessly outnumbered Spider-Man and Black Cat.
Despite the odds, Spider-Man and the Black Cat fought back in a heroic last stand. Before the two could be killed, salvation arrived in the form of Captain America, Iron Man, Daredevil, Hank Pym and the Fantastic Four, who struck back at the villains. Spider-Man's wife, Mary Jane Watson-Parker, had called S.H.I.E.L.D. to aid him, as she feared he was heading into a trap. A furious Green Goblin rocketed away and kidnapped her, and Spider-Man pursued him, fighting off Venom, who was trying to stop him. Spider-Man and the Goblin clashed once again upon a bridge (not the one where Gwen Stacy was killed), this time with Mary Jane's life at stake.
Finally Osborn gave a vital clue as to Aunt May's whereabouts, and was defeated by a combination of being shot by Mary Jane, struck by lightning, and attacked by Doctor Octopus, who was brainwashed by the police into trying to kill him. The Goblin fell into the river below, and Aunt May was found and saved.
In the aftermath, Peter received a pre-sent letter from Osborn, thanking him for all the "excitement" their rivalry has provided over the years and telling him to rest easy until they meet again. The rest of the Sinister Twelve were subdued by the heroes and arrested; Gargan ended up, ironically, in Osborn's old cell.
A new version of the Sinister Six apparently banded together during the Civil War but were stopped by Captain America and his Secret Avengers. 
Spider-Man, the Avengers, and the Fantastic Four later fight Doctor Octopus and his macro-octobot army. During that time, he had assembled another version of the Sinister Six consisting of Chameleon (who was posing as Steve Rogers), Electro, Mysterio, Rhino, and Sandman in a plot to slip the macro-octobot army into a military base and detonate them. 
After faking an attack in another time, Doc Ock managed to catch the attention of the Future Foundation, so he could enter the Baxter Building and steal some important pieces of technology. 
Ends of Earth
- And, well, there's a number of guys I've been getting ready for-- for some time actually. Six of 'em.
As a part of Doc Ock's last plan, the Sinister Six defeated the group of genius supervillains called Intelligencia and stole their Zero Cannon, a powerful weapon which change Earth's gravity field to send specific objects to space.
Time later, Doctor Octopus, in his plan to be remembered as the man who saved Earth, offered the chance to stop the Greenhouse effect, as well as speed it up, using a special device connected with different satellites on the orbit.
Disguised as Al Gore, Chameleon tried to accelerate the decision of world's leaders about the matter, but was uncovered by Spider-Man, who irrupted the scene along the Avengers. When the Chameleon was freed, he arrived in the Mediterranean on a meeting with the rest of the team. The Avengers followed them and arrived, fighting the Sinister Six, but they where all defeated by the villains, the price of the battle was Electro, who was sent to space by Thor.
Using an explosion as a distraction, Silver Sable saved Spider-Man and Black Widow. When they tried to get to one of Octavius manufacturing plants of satellites, they defeated Sandman, but Octavius asked for help to all nations, due his position in the matter, to capture Spider-Man.
While Spider-Man and his allies continue to disarm Doc Ock's bases, defeating Rhino in the process, they are attacked by S.H.I.E.L.D. forces before they can capture him and are forced to flee. Octavius asked for help of other super villains to watch over his facilities over the Wolrd, but even after Spider-Man tracks fown the final one, Octavius reveals he was going to destroy the World anyways, rather than save it. He activated his Octavian Lens, burning half of the World, including Silver Sable's country, Symkaria. But this is revealed to be a trick made by Mysterio (only burning a small portion of a city in Skymaria, while Chameleon uses a robot to fight Spider-Man, after they are defeated, Mysterio is convinced by Spider-Man to help him to catch the Octopus in his base in Guatemala, but Octavius used the mind-controlled Avengers as his new Sinister Six.
Spider-Man, Sable and Widow managed to defeat the Avengers, then he and Sable headed to Octavius underwater base. They are faced by Rhino while the base started to flood, he trapped Sable and left Spider-Man with two choices, to continue to fight him in order to save Sable from drowning (but the Octavius would activate the lenses) or let him drown himself and Sable but stop Octopus. After leaving Sable to her death at her request, Spidey managed to destroy Octavius's arms and equipment before taking his foe away to a doctor.
Superior Foes of Spider-Man
- So what do we got, you ask? Well, let’s see— there’s the pretty boy driver— Overdrive. A pretty girl thief— Beetle. The new one. An advance guy who specializes in being the pain in the butt… in a room full of pains in the butt. Speed Demon. Obviously. Oh, right. And a coward. You always gotta have one of those. Thanks, Shocker. Together, we’re the new Sinister Six. And yes, I am aware there are only five of us, thank you.
Months after that event, Boomerang and some other super-villains decided to form a group as the "all-new" Sinister Six. They fought Spider-Man (Otto Octavius in the body of Peter Parker at the time), who captured one of their members, The Living Brain, reprogramming it to serve him. Boomerang continued to call the team the "Sinister Six" in absence of a sixth member, reasoning "what's a better deal than being the Sinister Six, but only splitting the money five ways?" Boomerang directed the team on various heists for his own self-serving ulterior motives, at one point recruiting a small army of super-villains with the help of Owl's connections and calling it the "Sinister Sixteen." The team eventually broke up after Boomerang had thoroughly screwed everyone over, including himself.
All-New Sinister Six
A new incarnation of the Sinister Six appeared, dubbing themselves the "All-New Sinister Six", consisting of 8-Ball, Delilah, Killer Shrike, Melter, Squid, with Swarm as the leader. This incarnation was fought by Spider-Man and the students of the Jean Grey School, and ended with Swarm being defeated by Hellion, causing the rest of the Sinister Six to surrender.
- Original Line-up: Dr. Octopus (leader), the Vulture, the Sandman, Electro, Mysterio, and Kraven the Hunter
- Second Line-up: Dr. Octopus (leader), Electro, the Hobgoblin, Mysterio, the Sandman, and the Vulture
- Third Line-up: Dr. Octopus (leader), Mysterio, the Vulture, the Hobgoblin, Electro, and Gog (replaced the Sandman).
- Mysterio's Sinister Seven: Mysterio (leader), the Beetle, Scorpia, the Hobgoblin, Electro, the Shocker, and the Vulture
- Sandman's Sinister Six: The Sandman (leader), the Vulture, Electro, Kraven the Hunter, Mysterio, and Venom (replaced Dr. Octopus, whom the others were planning to kill.)
- Sinister Twelve: The Green Goblin (leader), the Vulture, the Chameleon, the Sandman, the Lizard, Electro, Venom, the Shocker, Hammerhead, Hydro-Man, Tombstone, and the Boomerang
- Fourth Line-up: Dr. Octopus (leader), Mysterio, the Chameleon, Rhino, Electro, and Sandman
- Fifth Line-up: Boomerang (leader), Speed Demon, Overdrive, Beetle, Shocker, The Living Brain
- Sinister Sixteen: Boomerang (leader), Speed Demon, Overdrive, Beetle, Armadillo, Bi-Beast, Clown, Cyclone, Fly, Kangaroo, Man Mountain Marko, Mirage, Scorcher, Shriek, Spot, Squid
- Superior Six: Superior Spider-Man (controller), Electro, Sandman, Vulture, Mysterion, Chameleon
- Eight Line-up: Swarm (leader), 8-Ball, Delilah, Killer Shrike, Melter, Squid
Equipment: None known.
Transportation: None known.
Weapons: Each teammates' arsenal
- According to Spider-Man, Mysterio was the one to come up with the name "Sinister Six."
- No trivia.
- 85 Sinister Six (Earth-616) Members
- 87 Appearances of Sinister Six (Earth-616)
- 5 Minor Appearances of Sinister Six (Earth-616)
- 25 Media Sinister Six (Earth-616) was Mentioned in
- 24 Images that include Sinister Six (Earth-616)
- Team Gallery: Sinister Six (Earth-616)
- ↑ Amazing Spider-Man Annual #1
- ↑ Amazing Spider-Man #334-339
- ↑ Spider-Man #18-23
- ↑ Spider-Man: Funeral for an Octopus #1-3
- ↑ Spider-Man Unlimited #9
- ↑ Amazing Spider-Man Vol 2 #12
- ↑ Peter Parker: Spider-Man Vol 2 #12
- ↑ It was revealed that most super-villains have corporate funding in the Marvel Universe
- ↑ Marvel Knights Spider-Man #10-12
- ↑ Civil War #2
- ↑ Amazing Spider-Man #648
- ↑ Amazing Spider-Man #659
- ↑ Amazing Spider-Man #682
- ↑ Superior Spider-Man #1
- ↑ The Superior Foes of Spider-Man #12
- ↑ The Superior Foes of Spider-Man #17
- ↑ 17.0 17.1 Spider-Man and the X-Men #4