It's four months later and Dean wakes in a pine box. He's been freed from Hell. He has a joyful reunion with Sam and Bobby, but it isn't long before the three wonder what exactly pulled Dean from Hell and what it will want in return.
Sam and Dean are stunned when the spirits of Meg and Agent Henricksen appear and accuse the Winchesters of failing them. Although rattled, the brothers must pull together to save Bobby, who is too crippled with guilt to fight off the angry ghosts of the young children he couldn't save.
Dean is transported back in time and is shocked when he lands in Lawrence, Kansas. However, that shock turns to amazement after he runs into a young John Winchester and Mary who have just fallen in love. Dean isn't sure why he was sent back so he begins to enjoy the time with his parents and newfound grandfather, who may be hiding a secret that is key to Sam and Dean's entire predicament.
Sam and Dean discover that Jack Montgomery, a family man, is turning into a Rugaru, a creature that starts as a human but changes into a flesh-eating monster. The people who are infected don't understand what is happening until they turn into cannibals and eat another person. Understanding what it is like to be a victim of a twisted destiny, Sam believes he can reason with Jack and convince him to control his urges. Dean doesn't think Jack's animalistic behavior can be subdued and decides the only honorable thing to do is to shoot him.
Dean and Sam investigate several murders at Oktoberfest. The first victim was found with bite marks on her neck, much like a vampire would leave, while the second victim has wounds that look like a werewolf attack. After a mummy rises from his crypt, Dean determines that a shape-shifter demon is terrorizing the town as iconic monsters from the old Hollywood movies.
Sam and Dean investigate the mysterious deaths of several men who apparently dropped dead of fright. They visit one of the victims in the morgue, and Dean becomes infected with the illness which starts as a general anxiety, then moves on to full-blown terror that eventually stops the heart. Sam and Bobby must find the root of the disease before Dean dies and is sent back to Hell.
It's a few days before Halloween and Sam and Dean investigate two mysterious deaths in a small town. The brothers find hex bags and deduce a witch is sacrificing people to summon a dangerous demon named Samhain. Castiel arrives in town and tells Sam and Dean the freeing of Samhain is one of the Seals that will lead to freeing Lucifer, so Castiel has brought a specialist angel named Uriel to smite the entire town.
Sam and Dean investigate a small town where the wishing well really works. A teddy bear comes to life, someone wins the lottery and the town geek gets a hot girlfriend. The brothers realize that while everyone is happy now, the end result will be disastrous.
Ruby tells Sam and Dean that a powerful demon named Alastair is searching for a girl named Anna who can hear the angels' conversations. The three set out to find Anna but once they do, Alastair attacks them and Ruby escapes with the girl. Believing they were set up, Dean lashes out at Sam for trusting Ruby, so Sam tells him what happened during those months Dean was in Hell and how Ruby saved his life. Castiel and Uriel return and demand to be taken to Anna but not for the reason Dean thinks.
Anna remembers her past and Sam and Dean finally understand why Castiel and Uriel want her dead. However, they disagree with the angels' orders and try to help Anna restore an important part of her past so she can be saved. Meanwhile, Alastair and his demons continue to close in on Anna and the brothers.
Sam and Dean investigate the appearance of a young female ghost in an abandoned house, but things become more complicated when a family moves in. The brothers fail to get the family to leave, but when the son is kidnapped though the walls, they look to Sam and Dean to rescue the boy.
A mysterious death draws Sam and Dean to a town full of old-school magicians. Their investigation leads them to Charlie, Jay and Vernon, three friends who were famous magicians in their day but have now been replaced by flashier, younger magicians. One of them has made a deal to acquire real magical powers, but the price was extremely high. Sam and Dean must figure out a way to reverse the spell before others are harmed.
Sam and Dean go undercover to investigate a string of murders at their old high school. The case causes them to flashback to their time there recalling how Sam was picked on by the school bully while Dean was Mr. Popular.
Sam and Dean enter a small town in Iowa, where three men have inexplicably beaten their wives to death. The guys realize that behind the murders is a Siren, a creature that can take different forms and desperately needs love and compels people to destroy themselves as a show of devotion. The Siren eventually puts Sam and Dean under their spell and pits the two brothers against each other in a fight to the death.
Sam and Dean investigate a small town where people are cheating death. They discover the Reapers have gone missing so they turn to Pamela for help. She sends them into the spiritual world to find answers and they come face to face with Alastair, who has been kidnapping all the Reapers in order to break another seal.
Someone found Lucifer's sword and is using it to kill angels. Castiel and Uriel have captured Alastair and ask Dean to use the torturing skills he learned in Hell to extract information from him so they can stop the murders. Sam is concerned Dean can't handle the job but Dean agrees to do it. However, when Alastair reveals some shocking information, Dean's world is shattered.
What if the Winchesters weren't hunters?
Dean and Sam are living very normal and separate lives. Dean is a corporate man who enjoys health drinks and listens to news radio vs. rock stations. He works at a company called Sandover Bridge & Iron Company alongside Sam who is in Tech Support. It seems as if the two do not know each other. However, after co-workers start committing suicide at an alarming rate, the two find themselves working side by side to solve the murders.
Sam and Dean are shocked to discover a series of comic books titled "Supernatural" that accurately detail their lives as demon hunters. They track down the writer, Carver Edlund, who explains he has visions of the brothers that he then turns into comic books. Chuck reveals that Lilith is coming and she has a plan for Sam.
A 19-year-old boy named Adam calls Sam and Dean looking for John Winchester, claiming to be his son. Dean and Sam meet Adam, assuming he's a demon trying to lure then into a trap. However, they find out that John was indeed the boy's father and Adam tells them of his "normal" upbringing, which infuriates Dean.
Castiel appears to Dean in a dream and says he has something important to tell him but they need to meet somewhere private. Dean and Sam go searching for Castiel but instead find Jimmy, Castiel's human vessel, who has only a spotty recollection of being an angel. Jimmy wants to return to his family and normal life, but Dean and Sam are concerned about his safety.
Dean and Bobby lock Sam in Bobby's panic room so he can detox from the demon blood. However, as Bobby sees more seals are being broken he tells Dean they should let Sam out to help them fight the impending apocalypse. Dean disagrees and goes to Castiel for help. Sam and Dean have a big blowout confrontation.
The apocalypse is coming, and Sam and Dean prepare for the fight in very different ways. Sam joins Ruby on a final run to kill Lilith, while Castiel and Zachariah tell Dean it's time to play his part in stopping Lucifer.