Season 10 begins with Sam’s frantic search for his missing brother, who is gone without a trace. The road to recovering the wayward Dean takes Sam down dark paths, with consequences that will shake the boys to their core. Meanwhile, Castiel has to pick up the pieces in the aftermath of Metatron’s campaign. With his grace failing and rogue angels still on the loose, Cas will face the ticking clock of his own mortality as all-new threats emerge to once again push all of our heroes to their limits.
Dean is a demon and running amuck with Crowley while Sam tries to figure out what happened to his brother. Meanwhile, Castiel is dealing with his fading grace.
Crowley is worried that Dean, driven by the mark, is getting out of control. Sam struggles to escape from Cole. Hannah tries to convince Metatron to give Castiel his grace back.
Sam continues to try to save Dean from the Mark of Cain. Realizing that Dean's antics are causing problems for him in hell, Crowley seeks help from a reluctant Castiel.
Sam and Dean investigate a series of werewolf attacks.
Sam and Dean investigate a haunting at a theatre.
After Dean hears a surprising message on Bobby's phone, he and Sam head out to investigate.
Sam and Dean discover a group of witches on a gone wild trip and attempt to stop them.
Sheriff Jody Mills is matched with an overeager partner during a mandatory sheriff's retreat and when a gruesome corpse is discovered, Jody calls Sam and Dean to help investigate.
Castiel finds Jimmy’s daughter Claire in a group home and she convinces him to break her out. After she runs away from him, Castiel calls Sam and Dean to help find her before she gets in trouble.
After the massacre at the ranch, Dean, Sam, and Castiel double their efforts to find a cure for the Mark of Cain. Desperate, Castiel comes up with an idea that Sam deems the single worst idea he's ever heard. Meanwhile, Rowena continues to plot against Crowley.
Sam is scanning the internet for suspicious paranormal activity and comes across a video of Charlie beating up a district attorney. Dean suspects she’s back from Oz and hunting on her own, assuming the district attorney must have been a demon.
Looking to get Dean out of the bunker, Sam finds a case for him and Dean to investigate – people are disappearing into thin air with only their clothes left behind.
A ghost starts killing people through various electronic devices. Sam and Dean discover who was killed and why this ghost is seeking revenge on a group of college students but what they can't figure out is how he’s doing it. With three dead, the brothers must stop the ghost before he claims his next victim.
Dean, Sam and Castiel deal with Cain’s return. Crowley and Rowena continue to grow closer but when Crowley bails on plans with his mother to help the Winchesters, Rowena lets him have it.
Despite Dean's directive to forget about looking for a cure for the Mark of Cain, Sam continues to do research. Dean suspects Sam is hiding something but decides to focus on a new murder case where they run into Cole. The three team up and learn a Khan worm is infecting men and turning them into murderers. Unfortunately, the worm makes its way into Cole.
Sam and Dean investigate a string of suicides committed by people with little in common other than the identical, grisly method of death – slow, self-administered disembowlment. All of the victims were members of a Catholic church and had recently given confession, leading the brothers to suspect the priest is somehow involved. Meanwhile, when Crowley captures Olivette, the leader of the Grand Coven, Rowena pleads her case to be allowed to practice magic freely again.
Sam and Castiel follow up on a lead about the Mark of Cain. Dean and Rowena meet.
Charlie calls Sam and Dean to tell them she found the Book of the Dead which could help remove the Mark of Cain. The Winchesters race to her after she tells them she’s been shot by a man named Jacob Styne who says the book belongs to his family and he won’t rest until he gets it back. Castiel and Metatron take a road trip to find Castiel’s grace but they hit a couple road bumps along the way.
Sam learns that former Men of Letters, Magnus, once built a magical box and Sam sets out to find it in the hopes it can cure Dean of the Mark of Cain. However, what he’s not prepared for is the deadly alarm system Magnus set up on the box. When Sam opens the box, he puts both his and Dean’s life in danger.
When Claire Novak gets a lead on her mother, Amelia, who has been missing for years, Castiel asks Sam and Dean to help her. However, when they find out what took Amelia, they realize there is a chance Claire may not get her happy ending.
Dean and Sam investigate a bizarre murder and realize the killer bears the same tattoo as those from the Styne family. Meanwhile, Castiel acts as referee when Charlie and Rowena are forced to work together on the Book of the Damned. When Crowley discovers that his mother is missing, he turns to an old enemy for help.
When it comes to the Stynes, Dean decides to take matters into his own hands. Sam tries to come to terms with his decision.
Dean makes a shocking decision regarding the Mark of Cain that would change not only his life, but Sam’s too. Meanwhile, Crowley and Rowena face off and Castiel gets caught in the middle.
