Due to the often illegal nature their actions as hunters take, Sam and Dean Winchester become wanted by the FBI for numerous crimes. The two are chased by FBI agent Victor Henriksen who refuses to believe in their stories of monsters and instead sees the Winchesters as deranged killers.
In an attempt to get out of her crossroads deal, Bela Talbot steals the Colt from the Winchesters. To buy herself time to escape, Bela lures the Winchesters to Monument, Colorado and sets them up to be arrested by Henriksen and the Monument Sheriff's Department.
After capturing the Winchesters, Agent Victor Henriksen alerts his boss, Deputy Director Steven Groves who decides to send a helicopter rather than risk transporting the Winchesters to Supermax prison by bus. As Henriksen, gloats to the Winchesters about his victory over them, Groves arrives and gives Henriksen paperwork to do while he goes to see the Winchesters.
Groves greets the Winchesters, telling them that he's pleased to see them and has been waiting a long time for them to come out of the woodwork. Suddenly, Groves draws a silenced pistol and shoots Dean in the shoulder. Before he can do more, Sam grabs the gun through the bars and he and Groves struggle over it. During the struggle, Groves' eyes turn black, revealing that he's possessed by a demon. Noticing this, Sam begins an exorcism, but the demon flees Groves' body through the vent system before Sam can finish exorcising him. Before departing Groves, the demon warns the Winchesters that "its gonna be a long night fellas."
Hearing the commotion, Henriksen, Agent Calvin Reidy, Sheriff Melvin Dodd and Deputy Phil Amici investigate to find Groves dead and Sam holding a gun. Sam insists that they didn't kill Groves and that they check the body for bullet wounds. When Phil finds none, Dean tells the agents and officers that Groves has likely been dead for months and Groves was possessed. Henriksen refuses to believe the Winchesters claims and orders Reidy to fire up the helicopter so they can leave with the Winchesters immediately. However, Reidy gets no response when he attempts to contact the helicopter pilot and emerges to find the four deputies with their throats slashed and the pilot dead as well. Reidy warns Henriksen that he thinks everyone is dead before the helicopter suddenly explodes. As Reidy recovers from the explosion, he turns around to find one of the dead officers now possessed. The possessed officer apparently tears Reidy apart, killing him.
In the aftermath of the explosion, Dodd and Phil arm themselves with shotguns while secretary Nancy Fitzgerald discovers that all communications are out. Shortly afterwards, the power goes out except for emergency lights which causes the Winchesters to realize that something is terribly wrong. While Dodd insists on going outside to check on the deputies and Reidy, Henriksen refuses, realizing that they are under siege and need to barricade themselves inside the station. Henriksen demands answers from the Winchesters about what's going on, believing that the events are an attempt by the Winchesters' "psycho friends" to break them out through a bloodbath. The Winchesters attempt to convince Henriksen that they are not responsible, but he refuses to listen to them about it being demons.
After Henriksen departs, Sam spots Nancy hiding in the doorway and convinces her to bring them a towel to treat Dean's wounded shoulder. When Nancy hands Sam the towel, he pulls her arm through the bars until Phil threatens him with a shotgun. After Phil leaves, Sam reveals that he used the opportunity to steal Nancy's rosary beads and the Winchesters use them to turn the water in their toilet into holy water to use as a weapon against any demons that come after them.
As the Winchesters wait for something to happen, Dodd enters with the intention of fleeing to a SWAT facility in Boulder, Colorado. Henriksen refuses to leave and suddenly shoots Dodd in the head, killing him and revealing Henriksen to be possessed by the demon that had fled Groves. Before the demon can move against them, the Winchesters grab him and force Henriksen's head into the toilet bowl full of holy water. As Dean hold Phil back with Henriksen's gun, Sam performs an exorcism. Sam is able to exorcise the demon back to Hell, but not before he warns them that its too late as he's already called in other demons and they are already on their way.
Following the exorcism, Henriksen regains consciousness, stunned by the experience and the fact that he had murdered the sheriff. Henriksen explains that five minutes before he had been fine before some black smoke entered him. The Winchesters inform Henriksen that he was possessed and Dean returns Henriksen's gun. Now convinced that the Winchesters have been telling the truth all along, Henriksen releases them to prepare for the coming attack.
As Nancy treated Dean's injury, Sam began planting devil's traps around the station. While Henriksen and Phil attempted to arm themselves with shotguns, Dean warned that it would be ineffective. After Dean told them that they needed a lot of salt, Nancy directed them to the road salt in the storeroom which Dean directed to be laid at every window and door. As Sam, Henriksen, Phil and Nancy laid down defenses, Dean headed out to the station's impound lot to collect supplies from the Impala. As Dean finished, a massive cloud of demon smoke appeared and Dean quickly retreated into the station.
Getting inside just ahead of the smoke, Dean warned everyone that the demons were coming. The demon smoke slammed against and covered the police station, causing the emergency lights to flicker, but were unable to penetrate the completed defenses. Finally, the demon smoke left and Dean began passing out anti-possession charms to keep the others safe when the demons inevitably returned.
While the group prepares for the demons return, Nancy spots Jenna Rubner outside along with about thirty other townspeople. Sam quickly realized that the people were now possessed by the demon smoke that had previously been unable to get in. Unnoticed, while staring out a window, Phil accidentally broke a salt line preventing demons from getting in by that method.
As Dean and Henriksen bonded while loading shotguns with salt rounds, the group heard a window breaking and found that Ruby had managed to get in through the window Phil accidentally broke the salt line of and got stuck in a devil's trap. While the others are not happy to see Ruby who killed her way in, Sam released her from the devil's trap and fixed the broken salt line. Ruby then informed the group that there were "thirty at least" demons outside "so far." Ruby revealed that demons were working for a new leader named Lilith that Sam knew about and never mentioned to Dean. After Ruby stated that they would need the Colt, Sam reluctantly informed her that it had been stolen. Upset, Ruby informed the group that she knew of one other way to get them out: a spell that would vaporize every demon in a one-mile radius, Ruby included. However, for the spell to work, Ruby needed to cut out the heart of a virgin: Nancy. While Dean and Henriksen protested, Ruby insisted that it was the only way. After Ruby told her that the spell would blow the demons out of their vessels and the people would survive if they hadn't been fatally injured already, Nancy agreed, seeing it as the best way to save her possessed friends.
Seeing that Sam wasn't objecting to the plan, Dean pulled him aside to learn that Sam thought the plan feasible as the thirty possessed people would die as well if they didn't do anything. Dean was horrified by the idea and told Sam that he had another plan that he wasn't sure would work, but thought was better than sacrificing a virgin. Questioned on his plan, Dean told Sam "open the doors. Let em all in. And we fight." Dean's plan was to lure all of the demons inside of the station, trap them and use the station's PA system to perform a mass exorcism. Per Dean's plan, Sam got the PA system to work on the emergency power and made a tape exorcism with Sam reciting an exorcism for use. However, Ruby refused to help, believing that they would die and asked to go. The Winchesters broke the salt line and devil's trap by a door and allowed Ruby to leave. Ruby threatened the demons outside with her demon-killing knife and they allowed her to depart.
Once Ruby left, the Winchesters and Henriksen each opened one of the doors into the station, broke the devil's traps and salt lines. The attack started when a demon swung down from the top of the doorway and kicked Henriksen to the ground. As two demons entered through Dean's door, he blasted them both with a sawed-off shotgun while Sam blasted the possessed deputy as he entered before being grabbed from the side by another demon. As the demon shoved him up against the wall hard enough to break the plaster, Henriksen threw holy water in the demon's face and escaped his grasp. As Sam recovered his shotgun and used it as a melee weapon to fend off demons, Dean and Henriksen fought back to back for a moment, blasting demons with their shotguns before going their separate ways as more demons entered the station.
As Dean used his shotgun to fend off demons, Sam continued to struggle to hold the ever-growing number of demons assaulting him back with blows from his shotgun. Getting overwhelmed Sam switched to splashing the demons with holy water, eventually joined by Dean. The two eventually ran out of holy water and were telekinetically pinned to the wall by the demon possessing Jenna Rubner. With all of the demons in the main room with them, Dean yelled to Henriksen "now." Fighting off demons, Henriksen activated the recorded exorcism over the PA system which caused the demons to writhe in pain.
On the roof, Phil and Nancy spotted that the demons had all entered the station and jumped off of the roof to spread salt lines along the outside of the doors and windows, trapping the demons within as the exorcism played. However, before they could finish salting the last door, the demon that had possessed the deputy emerged. After staring at Nancy for a moment, the demon chose to flee rather than kill Nancy and Phil helped her finish salting the door, leaving all of the demons inside the station trapped.
As the exorcism took effect and caused the demons great pain, they desperately tried to escape, but were unable to open the doors due to the salt lines laid down by Phil and Nancy. As the demons continued to desperately try to escape, the recorded exorcism forced them from their bodies. The demon smoke gathered near the celling, unable to escape the station with the salt lines surrounding it. Finally, the recorded exorcism ended and the demon smoke combusted into flame, killing all of the demons.
Following the end of the siege, the station's power returned and the possessed people all recovered. Now knowing the truth of what was in the world, Victor Henriksen decided to tell the FBI that the Winchesters had died in the helicopter explosion to get the law off of their backs. Shortly after they left, Lilith arrived, having been informed of the events by the Deputy Demon. Lilith proceeded to torture Henriksen, Deputy Phil Amici and Nancy Fitzgerald for 45 minutes before brutally killing them and destroying the station. The Winchesters learned of these events from Ruby the next morning. Ruby reminded the Winchesters that it was their plan that had the body count after all and supplied them with hex bags to keep Lilith off their trail.