Throughout fifteen years of Supernatural, Sam and Dean Winchester come across all manner of monsters, entities, deities, and everything in between, usually winning against them. However, they often find themselves in serious trouble on the way to victory, occasionally even getting possessed or controlled by their enemies.
A few different creatures have possessed the two over their time in Supernatural. On top of possession, though, certain creatures and special cases like the Mark of Cain control the brothers, making them monsters.
Both By The Wicked Witch
The Wicked Witch from Oz was one of the many wonders of the bunker, and after a nearly eighty-year entrapment, in "Slumber Party," the Wicked Witch broke free. Throughout the episode, with the use of her magic, she possessed the Winchester brothers.
What was especially wild about this was that the Wicked Witch possessed Sam, who, at the time, was inhabited by Gadreel. This led to some tense Dean moments as he scrambled to keep Charlie alive and his secret in place. The fact Charlie killed the Wicked Witch was another badass moment from the character who was killed off far too quickly. Even if nobody really believed the brothers were in danger, it was always fun seeing Charlie.
Dean By The Khan Worm
In "...And Then There Were None," Dean, Sam, Bobby, Rufus, Samuel, and Gwen all find themselves hunting the Khan Worm, another monster named by Dean - a hilarious running joke. Near the start of the hunt, Dean becomes infected and kills Gwen.
This surprisingly did not lead to that much tension, at least not as much as one would think with someone as hateable as Samuel involved. The Khan Worm was one of the few fun aspects of Eve's run on the show and resulted in some huge supporting deaths in Samuel and Rufus, the latter of whom was sorely missed. Seeing this amalgamation of characters was a unique, fun affair, and the tension born from the Khan Worm made it all the better.
Sam By Crowley
This is the only instance of possession and control that is actually done for good rather than for evil, murderous purposes, as Crowley agrees to possess the body of Sam inhabited by Gadreel to get Gadreel out of Sam's body.
An angel can only inhabit a human vessel with their permission, meaning they can cast the angel away by simply telling them to go. Crowley, as a demon, can forcefully enter and does so, finding Sam and convincing him to expel Gadreel. It was excruciating for Sam, as Crowley had to access the programming, the mind of Gadreel. Fairly selfless and nice from the King of Hell coming just before Crowley's time as a full-on ally to the brothers kicks off. When Gadreel left Sam, it resulted in a classic Sam/Dean fallout, one of the worst they had,
Sam By Gadreel
Gadreel's possession of Sam is the longest possession Sam endures during the fifteen years of Supernatural, going on for much of season 9. A significant reason for that is because Sam did not know about it, thanks to Dean.
Things got bad when Gadreel became an agent of Metatron and murdered Kevin Tran, the biggest moment of the storyline. The entire subplot of Dean allowing the angel to possess Sam was one of the most dividing moments between the brothers, riddling both brothers with guilt due to Kevin's death. Gadreel later admitted his mistakes and sacrificed himself for Castiel's goal, but that did not bring Kevin back, nor did it bring the brothers back together properly; it took Dean's death and hellish Knighthood to do that.
Dean By Michael
Of course, Sam was not the only one of the brothers possessed by an angel, nor the only one possessed by an archangel. In season 13, fans got to see something that was first mentioned a decade earlier, (alternate) Michael possessing his perfect vessel, Dean.
The whole arc was not Supernatural's best storyline. It gave audiences the very awkward and disappointing Michael vs. Lucifer duel, as well as a disappointing season finale cliffhanger image of a Michael freeze-frame. It did have its great moments, and seeing Jensen Ackles get to spread his (archangel) wings and play another character outside of Dean Winchester in the show was great. However were not too many consequences to the story, it was only the true focus for half a season as the show built up to its final season, and Lucifer's death never stuck.
Sam By Meg
Before she had a romance with Castiel and was an ally to the Winchesters, Meg very much hated the brothers, and hunters in general, making a grand attempt to cause their deaths in one of season 2's many great episodes, "Born Under A Bad Sign."
The episode sees Meg possess Sam, making him kill hunters in cold blood and kidnap Jo Harvelle. This being all the way back when she was working for Azazel. The possession only lasted an episode, but it was brilliantly done. The events of this episode led to the introduction of anti-possession charms for Sam and Dean, with this being their first experience of getting possessed in the show.
Dean By The Djinn
That was not the only time either of the brothers fell victim to a monster or demon in season 2, and it also was not the best one despite how awesome it was. In "What Is And What Should Never Be," named after the incredible Led Zeppelin song, Dean falls victim to a Djinn who showed him an alternate, apple-pie reality.
The episode is full of emotion and existential questions related to loss and Dean. It is only an episode-long story, but it is a fantastic episode. It is a story that highlights how Dean could never truly win. In the apple-pie life, he may be peaceful, but he is without a good relationship with Sam and no idealization of Mary. With his life, he has lost everything but Sam but still holds Mary in the highest regard.
Sam By Demon Blood & Ruby
Sam Winchester's ties to demons and demon blood were established early in Supernatural, as fans learned Azazel fed Sam drops of demon blood at birth. Even after Azazel's death, though, Sam remained in a storyline with demon blood.
Sam did some horrible things while hooked on demon blood, a story that dominated much of season 4. While this was undoubtedly all done by choice, Ruby had him in the palm of her hand. The combination of that and his addiction to the substance most definitely clouded his mind and nearly caused the end of the world and the end of his relationship with Dean.
Sam By Lucifer
Sam eventually stopped using demon blood, but even after he stopped being hooked on it, he had to use it again, drinking gallons of it. Hence, his body had the power to act as a vessel for Lucifer in arguably Supernatural's greatest episode, "Swan Song."
Sam was in a mental wrestling match with Lucifer as both tried to maintain control of Sam's body, Lucifer so he could fight and defeat Michael, and Sam so he could jump in the pit of Hell. It is undoubtedly one of the best instances of either brother being possessed by an angel, demon, or monster. The importance of this possession was of the utmost. It prevented the apocalypse and ushered in a new era of Supernatural without Eric Kripke.
Dean By The Mark Of Cain
The longest-lasting control and/or possession of one of the Winchester brothers came when Dean Winchester accepted the Mark of Cain from Cain in season 9 and did not get rid of it until the season 10 finale.
Through the Mark of Cain, fans were given Deanmon, and an angrier, more vicious, more murderous Dean Winchester who did things far removed from the Dean fans know and love. It was hard for all characters who saw the Mark take over Dean and control him, but it was a time that had some shocking and even brilliant moments for fans, like when demon Dean first opened his eyes.