Despite Dean's directive to forget about looking for a cure for the MOC, Sam continues to do research. Dean suspects Sam is hiding something but decides to focus on a murder case where they run into Cole.
Dean and Bobby investigate the disappearance of teenage girls when Sam awakes after recovering his mended soul. Bobby still does not trust Sam and Dean and his brother travel to investigate further. They find that the abducted girls are virgins and that dragons are the responsible for the kidnappings. Dean calls Bobby and he tells the name of a specialist that may teach them how to vanquish the dragon. While Sam searches where the dragon might be hidden, Dean visits Dr. Eleanor Visyak that tells him that he needs a blade forged with dragon blood. Dean borrows a piece ...
Sam receives a text about the disappearance of four young women and together with Dean, they head to Bristol, Rhode Island, to investigate the case. Sam has flashbacks with recollections from the town and he partially remembers that he had been in the spot one year ago to investigate missing men, and he believes that the cases are connected. The mystery increases when Dean discovers that Sam had had love affairs with the missing girls. When Sam meets the widow Brenna Dobbs, whose husband Sheriff Roy Dobbs had also disappeared, he finally recalls Arachne's case and ...
Dean and Sam travel to New Jersey to investigate a mysterious murder cases. However, Ben calls Dean and tells that it is an emergency situation and he heads to Lisa's house, leaving Sam alone. Sam discovers that the victims had played a prank on their colleague Rose and their deaths might have been caused by her revengeful ghost. Meanwhile Dean also learns what the "emergency situation" reported by Ben is about.
After a series of brutal murders, Dean, Sam and Bobby travel to investigate and they meet Rufus. They team-up and find that Eve, a.k.a. The Mother of All, is the responsible for the killings. When they find a clue of the location where she might be, they stumble upon Samuel and Gwen who are also chasing Eve. Soon they learn that Eve has created an evil worm that penetrates through the ear and force the victim to kill. Now they do not know who might have been possessed by the creature.
After a series of weird deaths in Chester, Pennsylvania, Dean and Sam discover that Balthazar has changed the history, avoiding the collision of the Titanic with an iceberg. Now Fate is intervening, murdering the descendants of those that should have died. The dilemma for the Winchester brothers is that Ellen and Jo are alive and if Castiel restores the time line, Ellen and Jo will be gone. Further, Castiel advises Dean and Sam that Fate is angry with them and they need to kill her to survive.
Lenore tells to Dean, Sam, Bobby and Castiel that Eve is in a small town in Oregon and they head to hunt her down. Soon they discover that the locals have been transformed in hybrid species of demons and Dean calls them "Jefferson Starships". When they meet the Mother of All, they discover a secret about Crowley.
Bobby tells Dean and Sam that Castiel has stolen the Moishe Campbell Diary, but he has a copy. They read the journal and discover that in 1937, H.P. Lovecraft had opened a gate to Purgatory with five worshipers of the devil. Meanwhile Crowley abducts Lisa and Ben to force Dean and Sam to step back. Sam summons Balthazar and the angel is surprised with the revelations about the partnership of Castiel with Balthazar. While Dean and Sam seek out Lisa and Ben, Bobby investigates what happened in 10 March 1937 and discovers the truth about his friend Ellie. Balthazar ...
Sam wanders with amnesia and chased by the police. While he tries to remember who he is, Dean and Bobby watch Sam that is in coma lying on a bed in Bobby's safe house. Dean and Bobby drive to the location where Castiel is; however, Crowley arrives with his new partner Raphael and requests the blood of the Purgatory woman to open the gate. Meanwhile Sam wakes-up and heads to meet Dean and Bobby.
Sam and Dean investigate the murders of mediums in Lily Dale, the most "psychic" town in America. They discover that an angry spirit is killing off the psychics, but in a town full of people who claim to be summoning spirits, they have a little trouble identifying the medium controlling the ghost.