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 the last reported sighting of the Hand of God. Lucifer sees the potential in getting his hands on this weapon so goes along as Castiel and sends Dean 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.
Dean sees an obituary notice for a wrestler he and Sam used to watch when they were kids. Deciding they need a break from tracking the Darkness, the brothers decide to attend the funeral to pay their respects. The funeral is full of wrestlers, including Shawn Harley, a hot shot new wrestler with a fiery temper who pushes everyone's buttons, and veteran wrestler Gunner Lawless. Sam and Dean attend the next match to re-live one of their fondest childhood memories but when another wrestler turns up dead, play time quickly turns to work.
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.
While Lucifer travels to Heaven to try to convince the angels to join him, Crowley recovers the Horn of Joshua and offers it to the Winchesters to defeat Amara... if they'll kill Castiel's body first.
Sam and Dean take a break from trying to find a way to rescue Castiel from Amara, and head to Colorado to investigate a series of mysterious disappearances. They turn up a strange race of creatures that prey on humans to breed, and a married pair of hunters.
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 try to get Chuck and Lucifer on the same page, and then create an army capable of weakening Amara long enough for Chuck to imprison her for eternity.
To kill Amara and restore the balance of light and dark, the team must gather hundreds of thousands of souls to make a bomb capable of destroying the First Darkness. However, someone will have to deliver it.