Crowley turns to Dean for help to locate the First Blade, the only weapon that can kill Abaddon. However, the trail leads them to the biblical Cain. Meanwhile, Sam asks Castiel for help when they need to extract the remaining angel grace from Sam's body to track Gadreel.

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.

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 case where people are suffering violent deaths after hearing a mysterious song.

Hoping to find a weapon powerful enough to defeat Amara, Dean convinces Castiel, who is still possessed by Lucifer, to send him back in time to 1944 to the fated submarine mission that sunk the Hand of God.

Sam and Dean face their biggest challenge yet. Rowena makes her move.

When hunters gather together to celebrate the life and tragic death of one of their own, Sam, Dean, and Mary must take action when a demon starts picking off hunters one by one.

Sam enlists Rowena’s help to track down an old world, powerful family of witches after Dean gets hit by a spell that is rapidly erasing his memory.

When multiple patients of grief counselor Mia Vallens turn up dead, Dean, Sam and Jack investigate the mystery surrounding the murders and, each inadvertently, are forced to deal with unresolved grief of their own.