After the Apocalypse is averted and Lucifer is imprisoned once more in his Cage, Crowley takes control of Hell, becoming its new King. However, as his position is not secure, Crowley forms an alliance with the angel Castiel who is trying to stop the archangel Raphael from ruling Heaven and restarting the Apocalypse. The two agree to work together to find Purgatory and use the monster souls there to ensure their rule over their respective domains. To this end, Crowley resurrects hunter Samuel Campbell and agrees to bring back his daughter in exchange for Samuel helping him to capture Alphas to interrogate for Purgatory's location. After Sam and Dean Winchester find out, Crowley claims to them that he holds control over Sam's soul to force them to aid him in his search for Purgatory by capturing monsters for him.
After dropping off a captured Rugaru to Crowley's demons, Dean becomes determined to force Crowley to give them Sam's soul and stop his efforts at finding Purgatory. After being captured by their old enemy Meg, Sam realizes that Meg is on the run from Crowley as she is a Lucifer loyalist and proposes an alliance: the Winchesters aid Meg in killing Crowley while she uses the torture skills she got from apprenticing under Alastair in Hell to get Crowley to give them back Sam's soul. Meg reluctantly agrees to the deal as she lacks the force necessary to take down Crowley on her own and leaves. After convincing Dean to work with Meg, Sam calls upon Castiel for extra help, pretending he knows where the Ark of the Covenant is to get Castiel to come. While Castiel initially refuses to help due to his war with Raphael even after Sam threatens him, Castiel eventually agrees and performs a spell to locate Crowley with no luck. As a result, the Winchesters and Castiel break into Samuel's compound to look for clues, but are caught by Samuel who refuses to help them. Samuel eventually explains his deal with Crowley and refuses to listen when Dean tries to convince him its a bad idea, eventually ordering them out. However, Samuel later comes to them with a map and shows them where to find Crowley's prison though he refuses to help them raid it. The Winchesters then call Meg and her demons with Sam killing one that is more interested in killing the Winchesters than Crowley to prove a point. While Meg originally wants the location of the prison and to go without them, Meg finally agrees to work together with the Winchesters and Castiel in the assault. As they pack up, Castiel warns Dean that he doesn't believe that getting Sam's soul back is a good idea due to it having been locked in the Cage with Michael and Lucifer for over a year where they have had nothing better to do than torture it. Castiel suggests that putting Sam's soul back in his body will result in dire consequences such as paralysis, insanity and psychic pain so strong Sam could be locked within himself for the rest of his life, but Dean is determined to press on, unaware that Sam has overheard the whole conversation.
The Winchesters and their allies arrive at the prison where Castiel lets them in a side door. Walking through the prison, they find the cells of several monsters including the djinn Brigitta who had tried to kill Dean before and continue on until they hear the sound of what appears to be dogs barking. Realizing its hellhounds, they flee through a door which they block and lay down a salt line in front of, but Meg's two minion demons are caught by the hellhounds and ripped apart. Telling the rest of the group that there are "lots" of hellhounds, Meg tries to vacate her vessel only to find that a spell cast by Crowley has locked her within her body. Sam draws the demon-killing knife and offers it to Meg to use to hold off the hellhounds while they go after Crowley, but Meg tells them that the knife is their best chance at killing Crowley. Meg kisses Castiel, using the distraction to steal his angel blade which she admits she doesn't know will work, but is willing to try to use it against the hellhounds. The Winchesters and Castiel leave to continue their search for Crowley, but Samuel uses an altered version of an angel banishing sigil to get rid of Castiel and the Winchesters are captured by Crowley and two demons. At the same time, Meg battles and kills the hellhounds with Castiel's angel blade but is then captured by the demon possessing Christian Campbell.
After their capture, the Winchesters are briefly locked in adjacent cells while Meg is tortured by Christian for answers on Crowley's orders. After Samuel attempts to explain himself, Dean is dragged away by Crowley's two demons to a kitchen where he is locked in with two ghouls. As Dean fights the ghouls, Sam bites open his own wrist and uses his blood to draw a devil's trap on the celling of his cell. When Crowley's two demons return for him, Sam draws them into his devil's trap and leaves them stuck in the cell. Sam reaches the kitchen where Dean is about to be killed in time to smash in one ghoul's head with a pipe and then impale the other one through the head with the pipe, killing them both. At the same time, Christian continues to torture Meg who merely mocks his efforts. As Christian tortures her, Meg suddenly starts laughing, causing Christian to question her actions. As Meg laughs that Dean is standing behind the demon, Dean snatches the demon-killing knife from Christian's hand and stabs him through the back with it, killing him. Dean then frees Meg from her bonds and they paint a devil's trap on the celling of the room.
Crowley attempts to interrogate Brigitta for information on the Alpha Djinn but is interrupted by the fire alarm going off. Annoyed, Crowley goes to the room where Meg was tortured to find her gone and Christian dead. Dean catches his attention by turning off the alarm, surprising Crowley as he believed that Dean would be dead by now. Sam hits Crowley over the head with a wrench, knocking the demon into their devil's trap which Crowley quickly realizes. Meg enters the room and she and Crowley insult each other before Meg makes Crowley cough up blood and tells him that Sam wants something from him. Sam demands his soul back to Meg's surprise and when Crowley refuses to talk, Dean has Meg make Crowley cough up blood again. Crowley finally tells them that he can't return Sam's soul and explains that he had a hard enough time getting Sam's body out and its impossible for him to go back into Lucifer's Cage and get his soul out too. Crowley questions why Sam even wants his soul back at all, telling him that Lucifer has had it to torture the whole time and taking it back would likely make Sam a drooling mess. Meg admits that Crowley is likely right and Sam tells Meg that Crowley is now hers. While Dean objects at first, Sam convinces him that Crowley is useless to them and Dean turns the demon-killing knife over to Meg, promising to let her back out of the devil's trap once Crowley is dead.
Meg enters the devil's trap and goes to kill Crowley, but he knocks her off of her feet, grabs the knife and throws it into the devil's trap, breaking the line and freeing him. Crowley then pins the Winchesters to the wall with telekinesis and holds the knife up to Meg, mocking her skill at torture. Before he can do anymore, Castiel teleports back in and demands Crowley let the Winchesters and Meg go. Crowley simply mocks Castiel and his war with Raphael until Castiel shows Crowley a bag containing the demon's human bones. While Crowley is shocked as he'd hidden the bones after Bobby used them to break his deal, Castiel tells Crowley he didn't hide the bones as well as he thought and demands to know if Crowley really can't restore Sam's soul. Crowley releases the Winchesters from his hold on them and tries to deflect the question but eventually admits that he really can't restore Sam's soul. Castiel then sets the bag of bones alight causing Crowley to go up in a pillar of fire before burning into a pile of ash, apparently killing him. Sam then retrieves the demon-killing knife from Crowley's ashes and realizing he intends to use it on her, Meg flees, leaving Dean disappointed as he wanted to kill her as well.
Outside, Castiel admits that his war with Raphael is not going well and on Sam's request, returns to the prison and kills all of the monsters within though, unknown to him, the Alpha Vampire manages to escape alive.
After the raid, Sam decides he doesn't want his soul back based on both Castiel and Crowley agreeing that the damage it sustained could leave him in bad shape. Despite this, Dean eventually makes a deal with Death to get Sam's soul restored.
Unknown to the Winchesters until months later, Crowley survives the raid as he and Castiel were actually working together and they faked his death. As a result, Crowley is able to continue his work towards capturing monsters and finding Purgatory undetected.
- Meg's use of an angel blade to kill hellhounds during the raid marks the first time an angel blade is used to kill anything except an angel. It is also the first time that a demon is shown using one. Meg later wields an angel blade in battle during Reading Is Fundamental and Goodbye Stranger, those times against angels and demons respectively.
- While the Winchesters alliance with Meg ends when Crowley is "killed", Meg later returns in The Born-Again Identity and allies herself with the Winchesters once more. She remains their ally until her death during the Hunt for the Angel Tablet at the hands of Crowley.
- During the raid, Meg kisses Castiel to get his angel blade and he returns the kiss rather enthusiastically. In Goodbye Stranger, Meg references this kiss when talking to Castiel about their history together and they are both shown to enjoy the memory of it.