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Picking up where the finale left off, Sam and Dean must deal with the Darkness that has been unleashed. Castiel deals with the effects of Rowena’s spell and recalls his brutal battle with Crowley.
Dean helps Jenna, the deputy he met after the Darkness fell, get back home safely and then sets off to help Sam deal with a town infected by a mysterious and deadly gas. However, when Jenna falls into dangerous hands, she calls Dean for help and Sam tells him to go back to her. Unfortunately for Sam, he isn't able to handle the townspeople turned monsters as easily as he thought.
While Rowena tries to consolidate her power to protect herself from the Winchesters, Sam and Dean search for a missing baby connected to the Darkness. Meanwhile, Castiel struggles to heal and Crowley tries to find a way to use the Darkness for his own personal gain.
Seen entirely from the point of view of the Impala, Sam and Dean go on a road trip to fight monsters and demons.
Sam and Dean investigate a series of murders at a local B&B that also happens to be Lizzie Borden’s old home. When a local man, Len, tells them he saw a little girl around the B&B around the time of the murders, the brothers realize Amara may be responsible.
Castiel seeks out Metatron’s help to stop the Darkness. However, Metatron is pretty happy with his new life as a freelance videographer for the local news and isn’t inclined to help the Winchesters or Castiel. Meanwhile, Crowley is losing his hold on Amara.
Sheriff Donna calls Sam and Dean for help after a horrific murder with supernatural elements happens in her town. Sam continues to have visions and asks God for help, which frustrates Dean.
Sam is shocked when his childhood imaginary friend Sully makes an unexpected appearance. Sam can’t understand why he’d see Sully now but what’s even more surprising is that Dean can see him, too. Flashbacks reveal young Sam’s friendship with Sully and why he needed him.
Amara unleashes her power on the local townspeople as she issues a shocking challenge. Dean tries to better understand the hold Amara has on him, while Sam and Crowley come up with a plan that could have disastrous consequences.
Now that he has Sam in the cage with him, Lucifer offers Sam a way out but it comes with a steep price. Dean and Castiel look into the angel smiting that could have killed Amara.
Sam and Dean investigate a case where people are suffering violent deaths after hearing a mysterious song.
Sam and Dean drop in on Jody Mills, Claire and Alex after receiving a panicked phone call from Claire. She believes the recent murders in town are supernatural and wants the boys’ help. However, Sheriff Mills tells Sam and Dean that Claire has been getting into trouble lately as she’s been attacking normal people and accusing them of being monsters.
Sam and Dean investigate a set of murders on Valentine’s Day and discover they are dealing with an ancient curse. Once kissed by the curse, the person is marked to die.
Hoping to find a weapon powerful enough to defeat Amara, Dean convinces “Castiel,” who is still Lucifer, to send him back in time to 1944 to the fated submarine mission that sunk the Hand of God. Meanwhile, continuing his charade with Sam while they wait for Dean’s return, Lucifer plans his next move.
Sam and Dean attend a wrestling match to relive one of their fondest memories but when a wrestler turns up dead they suspect foul play.
A dangerous creature is accidentally released into an old house, attacking a mother and her child, leaving them both in a coma. Sam and Dean learn that Bobby and Rufus once tracked the same entity so the Winchesters look to the past to come up with a plan to catch the monster before any one dies.
Sam and Dean battle a pair of werewolves who have captured two victims. Just as the brothers are about to win, one of the werewolves shoots Sam. Dean gets his brother and the victims out of the house but learns a pack of werewolves are hot on their tail, hoping to kill them all.
Lucifer takes a trip home and tries to assert himself into Heaven. Crowley tells Sam and Dean he has a way to take down Amara.
In a small town in Colorado, mysterious disappearances happen every 27 years. Sam and Dean head to the town to investigate and meet two hunters who have a personal vendetta against these once-in-a-generation monsters.
Amara unleashes a dark fog on a small town, causing everyone to go mad. Dean and Sam realize this is a stronger version of the original black vein virus Amara previously unleashed. They team up with the sheriff to protect the town but their old remedy no longer works. Meanwhile, Chuck returns with an interesting proposal.
Amara shows Dean how she’s torturing Lucifer. Worried for Castiel, Dean and Sam come up with a plan to rescue him from Amara’s clutches.
Sam and Dean face their biggest challenge yet. Rowena makes her move.
GOD VS. AMARA – God (guest star Rob Benedict) comes to a decision about Amara (guest star Emily Swallows) that has direct repercussions for Sam (Jared Padalecki) and Dean (Jensen Ackles).