Chicago is a city in the U.S. state of Illinois.
The boys arrive in Chicago to investigate recent violent deaths. Disguised as operators from a security alarm company, they visit the apartment of the last victim, Meredith, who was ripped to pieces as if by a wild animal. They discount werewolves due to it being the wrong time of the lunar cycle, and struggle to find clues until Dean notices that the blood spatter on the carpet forms a symbol. Sam and Dean also found Meg Masters in a bar of the city. After further investigation, the brothers realize that Meg may have a connection to the demon that killed their mom, and Dean calls his father and leaves a voicemail informing him about their situation. The boys take on Meg on their own and temporarily defeat her. They return to their motel and their dad reveals himself to them, but the daevas assault and they barely make it out alive. This marks the first major conflict between the Winchesters and demons. ("Shadow")
The demons released from the Devil's Gate head towards Chicago, and they begin possessing civilians along their way. A man in Oak Park, one of Chicago's suburbs located just west of the city, throws away his garbage in front of his house, and notices the demons flying through the night. Part of the Chicago skyline can be seen in the background. A demon heads towards him and the man tries to run back home, as if making it home would have even made a difference, but trips and ensuingly becomes possessed. The possessed man is next seen at a local department store and whispers his influence to a woman, causing her to kill another woman for a pair of shoes. The Winchester brothers and Bobby make their way there, thinking it could be a demon case, but find no evidence to indicate it to be so. They follow him anyway to a local bar that he supposedly enjoys spending time at, but Isaac and Tamara, a hunter couple they met earlier, beat them to it. The boys and Bobby break in too late for Isaac as he is murdered by the demons, but are able to save Tamara and they drive to Bobby's house. ("The Magnificent Seven")
Dean searches for possible cases he and Sam can work on, and he mentions "Chi-town," a nickname for Chicago, as a location for one of the possible cases. ("Family Remains'")
Chicago was slated to be destroyed by Death on Lucifer's orders. However, Death decided to spare Chicago because he enjoyed the pizza there. A handful of citizens were killed by Death during his time here.
As Dean and Sam prepare to head for the company HQ in Chicago, Bobby reminds them that the Leviathans know their faces and suggests that they mail in his flask instead. The brothers hesitate and then finally admit that they're worried that Bobby will become enraged and attack Dick. They refuse to let him help, much to his surprise and shock, and head out for Chicago.
Mr. Vili visits G. Ball & Co Trust in Chicago to access a safe deposit box he has stored there for many years.
- Family Remains (mentioned only)
- The theme of Supernatural: Bloodlines is very similar to New Orleans in The Originals, where communities, both Supernatural and otherwise are struggling for dominion in a heavily populated city.