|Sam wakes up on a park bench when two policemen try to move him along. He has no memory of who or where he is, but his first instinct is to take the policemen down. Afterwards, he's running from a patrol car when he bursts through the back door of a bar and scares a bartender named Robin, who tells him that the bar is closed. When she learns that he has amnesia, however, she takes pity on him and tries to help.
Robin wants to take Sam to the hospital, but he refuses. He feels like he has to be somewhere - stop something. When he sees a book by H.P. Lovecraft in the bar, snippets of memory assault him. He sees flashes of Dean,Balthazar, and,Bobby who says something about Lovecraft. He doesn't recognize them, but the last thing he sees is the sign for a motel called the Nite Owl. When he and Robin look online, they learn that the motel is real and just two towns over. Robin offers to drive him and, when they arrive, Sam instinctively knows that he's staying in the room with the best escape route. Robin is disconcerted, even more so when Sam opens the door to his room with her credit card and she sees the papers and other evidence of Sam's hunting occupation all over the walls. When she finds a pile of fake IDs, she starts to leave, but Sam sees a newspaper clipping about a missing woman named Eleanor Visyak and collapses.
Sam remembers finding Eleanor bleeding from her stomach in an alley with Dean and Bobby. In his memory, he hears Eleanor tell them that Castiel and Crowley kidnapped and tortured her for information about opening a door to Purgatory. She broke when Castiel took over the interrogation and told them everything they wanted to know. Bobby asks Eleanor how close they are to getting in, and she tells him that they just have to wait for the lunar eclipse tomorrow, as they already have or can easily get what they need: the ritual, the blood of a virgin, and the blood of a "Purgatory native." Before she can tell them where Castiel and Crowley are, she dies, and Castiel appears. He tells them to stop interfering, but Dean refuses. Castiel tells him that if he backs down, he'll save Sam when everything's over, and then touches Sam's head, tearing down the wall in his head.
Sam snaps out of the vision, and Robin asks him what he remembers. He tells her that his name is Sam and that he was with two guys, one a "male model type" and one an older man named Bobby. He finds an address for Bobby in his contact book, takes the car keys on his desk, and goes outside with Robin. He instantly knows that the Impala is his car, and while Robin says her goodbyes, she warns him that he might not like what he finds if he goes to Sioux Falls. As they talk, Sam hears something and tackles Robin to the ground just in time to avoid being shot by someone who looks exactly like Sam.
While Sam and Robin drive to Sioux Falls, it is revealed that Sam is actually comatose and in a dream state as a result of Castiel touching his forehead and breaking the walls that Death created in his head. Dean and Bobby have put his unconscious body in Bobby's Panic Room, but they're running out of time if they want to stop Castiel from opening the door to Purgatory. When Balthazar appears and betrays Castiel by giving up Crowley's hiding place, they decide to leave Sam behind with a note that lets him know where they'll be.
Meanwhile, in Sam's head, Sam has another confrontation with his doppelganger, who reveals that Sam is actually unconscious after Castiel broke the wall in his mind. He learns that the doppelganger in his mind is "soulless" Sam, and that he intends to kill "soulful" Sam in order to take over his body in the real world. The two Sams play a cat and mouse game where "soulful" Sam emerges the victor. As he dies, "soulless" Sam tells him that there is another Sam, one that's worse than him. Sam then absorbs "soulless" Sam and regains his memories of the time he was soulless. He remembers that Robin is actually a victim of a demon attack, one who he mercilessly killed when the demon tried to use her as a hostage. After Sam apologizes for failing to help her, she disappears.
Back in the real world, Castiel meets with Crowley, who has assembled the necessary ingredients for their ritual. Castiel wants to renegotiate their deal. He will not give Crowley the souls, so Crowley can either flee or die. The demon leaves Castiel with the blood for the ritual.
Still trapped inside his head, Sam travels to Bobby's house and meets the third Sam, who is comprised of the memories of his time in Lucifer's Cage. "Tortured" Sam tries to convince Sam not to reabsorb him as he is not strong enough to face those memories, but Sam is adamant that he needs to wake up and help Dean and Bobby. "Tortured" Sam wishes him luck and then allows Sam to kill him. As he reintegrates into Sam's mind, Sam's physical body seizes out of control.
Later, Castiel confronts Balthazar. He says that Dean is coming, and someone among them is a traitor. Balthazar asks him who it is, and Castiel tells him that he doesn't know, but he wants Balthazar to investigate. While the other angel is distracted, Castiel stabs and kills him with an Angel Killing Sword.
Dean and Bobby arrive at Crowley's hideout and scope out the building. It's full of angels, but before they can try to infiltrate it, they are hit by an entire cloud of demons that flips the Impala with them inside it. Castiel is still preparing the ritual when the cloud of demons descends around the building, and Crowley appears. Castiel tries to kill him with his angelic touch, but it fails because Crowley has a new partner: Raphael. Castiel is surprised at the partnership because of their differing goals, but both Crowley and Raphael seem to think they have taken the best course available. They demand the blood; Castiel throws them the jar of blood and leaves. Outside, Sam surveys the flipped and empty Impala - has a flash of memory from Lucifer's Cage, then continues to approach the building.
Crowley conducts the ritual, and though Bobby and Dean try to interrupt, completes it. Nothing happens, and Castiel reappears. Crowley realizes that he switched the blood and conducted his own ritual. Castiel displays his new power briefly in a flash of energy and tells them that they cannot imagine what it is like to be filled with the power of "millions upon millions of souls." Crowley immediately beats a hasty retreat, but Raphael is unable to. A terrified Raphael begs for mercy, asking why Castiel allowed Crowley - a demon - to escape. Castiel answers that he has plans for Crowley, but none for Raphael. Castiel then snaps his fingers, completely obliterating Raphael.
He turns to Dean and Bobby. He was right, he says, and did save them. Dean nervously agrees, then suggests that Castiel should return the souls and disarm himself. Castiel says he has Raphael's followers to deal with. Dean is worried that Castiel's power is affecting his mind and that he could "kill us all." He reminds Castiel that he is family and tells him that he doesn't want to lose him. Castiel says that he has no family anymore; he will not give up the souls. Suddenly Sam stabs him from behind with an angel killing sword, but nothing happens. Castiel greets him, then says the sword will not work because he is not an angel anymore. He says that he is their new God - a better one - and that they must venerate him or be destroyed. They look at him in horror.