Season 11 opens right where we left off in Season 10's finale, or shortly thereafter. The Darkness has arrived. Sam wakes up in Baby where the Darkness has passed, and Dean is nowhere to be found. Sam remembers being stuck in the car with Dean as the Darkness rolls in, only to look over and see Dean has disappeared. We, then, catch up with Dean, who remembers being outside in the smoke of the Darkness, almost as if in the eye of the storm. Protected from the smoke and with something that appears to be the embodiment of the Darkness -- revealed to be… a woman! Dean wakes up in a field where Sam finds him about a mile away from the car. Dean gives Sam the lowdown on the Darkness, explaining that, though she wasn't much of a talker, she did thank him for setting her free.
We then cut to Cas, who is hunkered down in a barn still red-eyed and hopped up from Rowena's curse. He flashes back to killing Crowley but remembered seeing the demon smoke and recalls that Crowley survived. The family who owns the farm makes their way to the barn, and one of the boys carefully enters with a gun aimed at Cas. Cas warns him to run and that he doesn't want to hurt him. Cas makes a run for it and is chased by the family.
The boys comes across a dead roadwork crew on the road. As they investigate, a random road worker comes after them and is stopped by a sheriff. She holds the boys at gunpoint while they offer to show her their FBI badges. She says no she wants to see the skin on their neck so she knows they're not like the others. She reveals they are smack dab in the middle of what sounds like a zombie situation, and she was injured while hiding from them.
Sam and Dean take Sheriff Not-A-Zombie to the nearest hospital for wound care only to find another death scene. Dean sews up Sheriff Not-A-Zombie while Sam checks out the hospital to make sure they're in the clear. Like there was really any doubt they weren't?
Sam hears a baby crying and finds a zombie road crew worker trying to bang down the supply closet door where the crying is coming from. The zombie dies before he can get in. Sam discovers a man and a newborn baby in the supply closet.
We then cut back to Crowley's smoke which makes its way into a woman arriving to her home in the 'burbs with her groceries. Crowley discovers he doesn't have all his mojo and decides to go old school, grabbing the crowbar from the car and heading into the house. Before he can off the husband, he discovers the husband has invited over another couple, and they're about to have birthday orgy with the wife. Crowley sets down the crowbar…
Back at Zombie Hospital, the man from the supply closet explains that his wife died following childbirth, and, while he was outside taking it all in, the zombie road crew pulled up and started killing everyone in the hospital. He was able to rescue the baby and get to the supply closet, but not before he was infected. Sam, Dean, and Sheriff Still-Not-A-Zombie can see the zombie skin on his neck. He asks how long they think he has before he turns.
Meanwhile, back on the farm, a full-scale manhunt is on for Cas, including farmers and police (where exactly is he anyway?). He prays for his angel brother or sisters to please save him from doing worse than he already has.
The Soon-To-Be-A-Zombie man asks Sam and Dean to let him go if gives his baby to Sheriff Not-A-Zombie. They agree, and he gives her the baby and makes a run for it. Dean points out that will probably come back to bite them in the ass later. More zombies start showing up outside the hospital.
As they debate what to do, Cas calls Dean. He quickly says to tell Sam that Rowena got away with the Codex and the Book of the Damned. Dean reveals that the mark is gone and that the Darkness has been released and is a woman. Cas doesn't believe them and hangs up abruptly when two angels show up to answer his prayer.
Sam and Dean go back and forth about what to do, what they've done, and how it's time to change the pattern. Sam talks Dean into getting the Sheriff and Baby out of harm's way while Sam distracts the zombie guys. The plan starts strong, as Dean and the Sheriff make their way out of the hospital with the baby. Sam ends up hiding in the supply closet where he finds a zombie lady in waiting. Sam kills her but not before she infects Sam with the zombie blood. The zombies get in, and, when they see Sam's been infected, they leave him be.
Back in hell, the demon minions bring Crowley back to his original meat suit. The demons then break the news to Crowley that not only has the Darkness been released, which Crowley doesn't believe, but that there's trouble in the cage where Michael or Lucifer have been trying to warn the rest of hell. This has turned hell into a madhouse.
Elsewhere, the angels have brought Cas to a hidden room and reveal they have no intention of taking him back to heaven. It looks like some angel torture is about to begin.
Dean recalls the rest of the conversation with the Darkness. She explains that, because Dean never hurt her, she won't hurt him and that they are bound by the Mark of Cain forever. She lifts up her arm to reveal that she also has the Mark of Cain. Before we cut away, we see the Sheriff changing the baby's diaper only to reveal the baby has the Mark of Cain… She is the Darkness.