After learning of the state of Heaven, the Scribe of God and angel Metatron decided to get revenge for being forced out by the archangels millennia earlier by expelling all angels from Heaven. To this end, Metatron tricked the angel Castiel into helping him get the needed ingredients for his spell under the guise of fixing Heaven through the Angel Trials to seal up Heaven. Despite the interference of Naomi, Metatron succeeded in making the angels fall, taking Castiel's grace in the process and leaving him human. Metatron remained the only angel in Heaven following the Fall while the other angels had their wings burned off. Many also died falling to Earth.
Following the Fall, Castiel was left stranded in Longmont, Colorado as a human. While there, he encountered the angel Hael who showed him how angry the angels were with him, trying to force him to allow her to possess him by telling him that if the angels learned where Castiel was, they'd bring down a vengeance upon him that "would make God striking down Lucifer look like child's play." Castiel was forced to kill Hael in the end, but at the same time, angels attacked Dean looking for Castiel and proving Hael right. As Sam was dying from the effects of the Hell Trials, Dean was forced to allow the angel Gadreel, under the guise of dead angel Ezekiel, possess Sam in secret in order to heal him of the damage the Trials left him.
A few days after Falling, some of the angels under the command of Bartholomew begin looking for Castiel for revenge for his role in the Fall. Using the Reverend Buddy Boyle and his podcast, the angels reach out to religious people to start gaining vessels for themselves. Able to sense Castiel due to their powers as angels, Bartholomew's Assistant and another angel travel to St. Anne's Cathedral in Emory Park, Iowa where Castiel works during the day while staying at the St. Anne's Shelter for Men. There, the angels encounter two priests and torture them for information on Castiel, eventually leaving them with their eyes burned out and impaled on fence posts. They are unable to find Castiel himself however. Castiel, going by the name Clarence, finds the two priests bodies while at work the next day and quickly flees the shelter, realizing that the angels are onto him.
The same day Castiel finds the bodies, Gadreel takes control of Sam to tell Dean that he's picked up chatter on angel radio revealing that not all of the angels are wandering around in confusion and are now rapidly organizing into a faction who's angels are finding vessels to contain them and who's leader wants Castiel found. When Dean asks if Naomi leads the faction, Gadreel tells Dean he hasn't heard her name and Dean tells him to give back control to Sam and Dean will tell Gadreel if he needs him again. Gadreel does so and Dean tells Sam that since the angels are organizing, they are now even more dangerous and he and Sam have to locate Castiel before they do. Though Sam notices his slip-up in knowing that the angels are organizing, Dean simply claims that it makes sense that they are.
Now knowing that they need to find Castiel fast, the Winchesters pour over the information they have on where he is and a map Dean made of where he might've been able to get to in the days since the Fall. Searching the news in Longmont, Colorado where Castiel had landed, Sam finds an article on the murder of Gloria Lewellen Jacobson, Hael's vessel who was described as looking like she was blasted from the inside out. Dean realizes its an angel kill and that the angels either just missed Castiel or caught him. Sam then finds an article on the murders of the priests in Emory Park, Iowa and they realize as the men were tortured, the angels tortured them for information on Castiel as that is within the area Dean thinks Castiel could've gotten to within the time frame he had set up on his map.
That night Castiel goes to sleep on an abandoned bus in a homeless encampment in Lafayette, Indiana. An angel using a pharmacist from Dayton, Ohio who had listened to Buddy Boyle's podcast and said "yes" as his vessel tracks Castiel to the encampment. Castiel seemingly senses the angel and draws his angel blade, but is caught by surprise when the angel is able to get on the bus behind him. The angel slashes Castiel's shoulder with his own angel blade and is shocked to see it bleeding. The angel is shocked to realize Castiel is now human and Castiel takes the opportunity to stab the angel with his angel blade before he can react, killing him. Castiel then flees the encampment and hitches a ride on a Motor City Meats truck to Detroit, Michigan.
The Winchesters travel to St. Anne's Cathedral where Dean speaks to a homeless man who had known Castiel. Besides being able to tell Dean that Castiel is going by Clarence, left the day that the priests bodies were found and said he always had to keep moving, he is unable to tell Dean anything useful. In the meantime, Sam searches news articles for clues and finds one on the death of the pharmacist which they recognize as another angel kill and head to check it out.
In Detroit, Castiel decides to use his remaining money to get a tattoo that will prevent the angels from tracking him with their powers anymore. At the same time, Bartholomew's assistant reports to him on the success of their efforts to find vessels using Buddy Boyle and how their Dayton operative is tracking Castiel. Another angel arrives to inform them that the pharmacist angel had managed to track down Castiel, but Castiel managed to kill him. Bartholomew is left furious by this with his assistant telling him that Castiel is a madman and very dangerous. Bartholomew orders the two angels to find and kill Castiel, but the other angel informs him that it may not be possible as Castiel has found a way to ward himself against them and they can no longer track him. Needing another way to find Castiel, Bartholomew decides to hire rogue Reapers who are willing to freelance for a price and can hunt Castiel down through other ways than the angels ability to track people with their powers. Bartholomew meets with one Reaper in particular, Maurice and tells him to track Castiel by following the Winchesters.
Continuing their own search for Castiel, the Winchesters travel to Lafayette where they visit the police station in the guise of FBI agents investigating the pharmacist's weird "murder." The Winchesters go through the angel's things and find Buddy Boyle's podcast on the pharmacist's smartphone and watch it. Hearing Buddy Boyle's sermon, they realize that the angels are using him to recruit vessels for themselves since angels need permission to possess humans and find through a search of Buddy Boyle's website that he has influence over people around the globe. Unknown to them, Maurice is nearby watching them, hoping to use them to locate Castiel.
The Winchesters travel to the homeless encampment where Castiel had stayed and the pharmacist angel was killed. Though the homeless people are distrusting of them at first, they finally manage to get a man who had talked to Castiel shortly before he was attacked by the angel to talk to them. The man doesn't know much beyond that Castiel was seemingly on the run and that he is no longer at the encampment, but he is able to give them a clue: he saw Castiel boarding the Motor City Meats truck so he likely headed to Detroit. The two begin planning what to do once they reach Detroit, planning to search the homeless shelters and encampments, soup kitchens, anywhere Castiel might've gone to look for work, vagrancy arrests and odd deaths. As they discuss their plans, Maurice follows them, but the Winchesters notice the Reaper and capture him.
Having captured Maurice and recognizing him as a Reaper, Sam and Dean take him to an abandoned warehouse where they bind him and interrogate him by using an angel blade to torture him when he won't talk. Under torture, Maurice explains that he was sent to find Castiel as he has warded himself against the angels being able to sense him. When Sam asks if Naomi hired him, Maurice is amused that they don't know that Naomi is dead and informs them of that fact. Under further torture, he explains that Bartholomew, who he describes as Naomi's protégé and "an up-and-comer" hired him. Sam realizes that Bartholomew sent Maurice to follow them, believing the Winchesters could lead him to Castiel. When Dean asks if Bartholomew is the one organizing the angels now, Maurice doesn't answer despite more torture and insists that he's told them all he knows. Dean threatens to kill him, but Maurice tells Dean to go ahead as he may not have found Castiel, but there are other Reapers searching for him and they will find him. Believing Maurice, Dean stabs him through the throat with his angel blade, killing him.
In Detroit, Castiel meets a woman in a church and has a discussion with her about faith in which he tries to tell her the truth about God, Heaven and the angels, but she refuses to listen due to her faith and tells him to keep his own faith. He later digs through the garbage for food and meets a woman named April Kelly who sympathizes with him due to having gone through hard times herself and gives him her sandwich. That night, as she leaves work, April finds Castiel huddled from the rain and brings him home, telling him he looks like he's "been to Hell and back." Noticing Castiel's wound, April treats it, discussing with him what led to him getting the wound in the first place. Castiel tells her he killed the person who wounded him and he ended up where he is due to vanity leading him to believe he could fix everything which had led him to having to run now. After Castiel tells her that being alone and cold is new to him, April kisses him and they have sex. Afterwards, April comments that Castiel is carrying a heavy load for such a sweet guy and he tells her that he's done a lot of foolish and unwise things and he's no angel. April asks if the person he was wrong to trust can help him fix things, but he tells her that they are no longer in contact and that he hopes to continue their relationship when she asks him what he intends to do next.
After finding no clues to Castiel's location after searching all night, Dean decides to turn to Gadreel for help, eventually getting his attention. Gadreel takes control of Sam and Dean asks for his help. Gadreel insists that its too dangerous for him to directly help Dean in his search, but Dean just asks him to help him find Castiel, not physically do something. Gadreel informs Dean that he can't find Castiel anymore than the other angels can because he's warded, but Dean suggests a different solution: there might be a Reaper hunting him and he asks if Gadreel could find that instead. Gadreel agrees to try and locates the Reaper and Castiel. Sam and Dean then rush to April's apartment to help Castiel against the Reaper.
The next morning, Castiel wakes up to find April cutting up fruit and she tells him that she washed his things for him. Searching his jacket, Castiel finds his angel blade missing and when he asks April about it, she puts the angel blade to his throat in a threatening manner, revealing herself to be another rouge Reaper that was hunting for him and has now found him. April ties Castiel to a chair and explains that she didn't attack him right away as she was told he was dangerous and powerful and when she met him, he was armed so she decided she needed to earn his trust first before attacking as she needed information. She had sex with him for fun and because she found him attractive. Castiel asks who hired her since with Naomi dead, he thought things would be in chaos, but all April says is that there's a new sheriff in town and he hired a bunch of Reapers to search for Castiel and she got lucky. She then decides to stop answering his questions and get her own answered, asking Castiel about Metatron and torturing him for information using his angel blade. Castiel insists he knew nothing of Metatron's spell or plans and was cast out too like all of the other angels. April doesn't believe Castiel and continues to torture him while Castiel tells her that he was only working with Metatron to restore Heaven and bring the factions together and he was naïve. April knows Castiel was with Metatron when the spell was cast and demands to know more about the spell itself. Castiel continues to insist he had no idea Metatron was assembling a spell and that all he knows is that his grace was the final ingredient for it. Castiel tells April that Metatron stole his grace for the spell which is why he's now human, but April points out that he could've easily just given Metatron his grace instead. Castiel tells April that it may be unwise to kill him since his grace was the key to empowering the spell which means he may be the key to countering it.
At that moment, Sam and Dean burst in, having finally arrived to help. April quickly stabs Castiel in the chest with his own angel blade, killing him then turns to fight the Winchesters. Dean draws an angel blade of his own, but April uses telekinesis to fling him and Sam to opposite sides of the room, making Dean drop the angel blade which she kicks away. April goes after Sam as he gets up, knocking him out with one punch. While April's distracted, Dean grabs the angel blade from Castiel's chest and goes after her. As April turns to face him, Dean stabs her in the chest with Castiel's angel blade, killing her.
Dean checks on Castiel, but realizes that he's dead. Gadreel takes control of Sam again and uses his powers to heal Castiel's wounds, ultimately resurrecting him. Gadreel then returns Sam's body to the position it was left in when April knocked him out and Sam regains consciousness as Castiel comes back to life. As Sam and Castiel are aware of his death, Dean quickly lies and tells them that after Sam got knocked out, he made a deal with April not to kill her if she brought Castiel back. He tells them that she brought Castiel back and then he killed her. Castiel realizes Dean lied to April and he tells him that he did and he does that.
With Castiel now safe, Sam and Dean return to the Bunker with him and Sam questions Dean on how he was able to find Castiel in the first place. Dean lies that he went through Maurice's pockets, found an address and took a chance by searching there. Sam is suspicious, but Dean is able to brush off his concerns. Castiel tells them that he's happy to be at the Bunker and that he now understands that there's more to humanity than survival. In the process, Castiel reveals that he had sex with April to Sam and Dean's amusement. Castiel tells them that he is happy to have Sam and Dean for teachers about humanity, but when he goes to get more food, Gadreel takes over again and tells Dean that Castiel can't stay in the Bunker as he will bring the angels down on all of them. Though Dean points out that Castiel now has a warding tattoo, Gadreel tells him that Castiel had one when April found him and thus, nowhere is safe for him, especially as Bartholomew is massing a force and the can't withstand an incursion. Gadreel tells Dean that Castiel is in danger and if he is at the Bunker, so is Gadreel so one of them must leave. Dean points out that Gadreel can't leave without Sam dying as he isn't well enough to survive without Gadreel yet, but Gadreel refuses to relent. As a result, Dean is forced to ask Castiel to leave the Bunker. He later lies to Sam that Castiel chose to leave on his own as he felt they were in danger with him there.
Following his departure from the Bunker, Castiel continues to be hunted by angels, but none find him until they find him when tracking the angel Muriel. In that instance, Castiel steals the grace of the angel Theo, regains his status as an angel and escapes. He is later captured by angels loyal to Bartholomew who turns out to be a former subordinate of his who asks for Castiel's help in rallying the angels. After finding Bartholomew's methods too brutal, Castiel refuses and is forced to kill Bartholomew in self-defense. Afterwards, Bartholomew's angels stop hunting him, even offering to join him and Castiel eventually begins amassing his own faction to battle Metatron and retake Heaven.
- Castiel has sex for the first time with April Kelly who turns out to be possessed by a reaper. Sam and Dean are left amused by the news along with the fact that when they asked if he used protection, Castiel tells them that he had his angel blade as protection.
- Another sign that Gadreel is not who he says he is: he's scared of the other angels finding him and he doesn't want Castiel around who would be able to tell he's not Ezekiel.