- For more information about his crimes, see Ten Commandments Killer.
John Lowe was a homicide detective with the LAPD. His wife Alex has borne him two children, Holden and Scarlett. He first visited the Hotel Cortez while being drunk in 2010. Then, James March saw potential in him and started trying to make him his successor to finish his Ten Commandments murders. After five years, he agrees and starts committing murders. In the same year, Holden was abducted from a carnival in Santa Monica, which has caused a strain on his marriage.
Personality and Appearance
John remains dedicated to both work and family by strictly dividing the two, even if it means reading to his daughter through video chat while at the office. On the job, he has a keen eye for detail and a gift for profiling a criminal's motivation. As John begins to go insane, he becomes more vulnerable and confused, however after figuring out that he is the Ten Commandments Killer he gains a sense of clarity and begins to build his life up back together.
John documents a unique crime scene involving a dead woman impaled by a spear and locked in super-glue affixed coitus with a man who has had his eyes and tongue removed but left alive. Upon returning to the department, he reviews a case from a month earlier involving one Martin Gamboa, killed by blunt force trauma to the head with an unknown weapon and sexually assaulted by something (perhaps the weapon) that left traces of gold paint in his rectum. After handing over the old case to be cross-referenced with the new he receives a call from someone claiming responsibility for the murder and directing him to Room 64 at Hotel Cortez. At the hotel, he found nothing in Room 64 but an extremely inviting bed where he quickly fell asleep. Upon waking to a jazz playing clock-radio he discovered a young boy in the room resembling his abducted son. He gave chase through the halls but he was successfully evaded. An emergency text from his wife (actually a ruse) leads him to a home where he receives another anonymous call before seeing a mysterious figure and discovering the disemboweled corpses of two men hanging from their respective bedposts. To draw danger away from his family and give his wife time to grieve, John takes up temporary residence at Hotel Cortez. 
John Lowe finds another murder case of the Ten Commandments Killer - the editors of a gossip site are killed and their tongues are rather nailed-up or even taken out and thrown randomly around the room. After seeing this gruesome crime scene, he comes back to the hotel where he is "welcomed" by Gabriel who is dying and all covered in blood. He takes him to the hospital where he says that he didn't mean to kill her (referring to Claudia) but "the junkie whore" Sally instead. Therefore, he goes back to the hotel to question her but since he doesn't find out anything new, he decides to arrest her for trying to edit one of the Ten Commandments which he finds disrespectful and suspicious as well. While going down in the elevator, Sally seduces him and disappears. Later, his wife meets him at the hotel and asks for a divorce. After Alex takes him to his room and gives him medicine to have a rest, they make out but she stops and leaves.
Serial killers check into the Cortez, including Aileen Wuornos who meets John at the bar and attempts to kill him, only for him to subdue her and realize that multiple other killers have supposedly checked in. Refusing to believe this and only accepting that these people are wearing Halloween costumes and playing some cruel trick, Liz informs John about March's annual Devil's Night, a dinner where the most notorious American serial killers, who have previously checked into the hotel before their apprehension or death, come together and celebrate their crimes. At the dinner, John is introduced to John Wayne Gacy, the Zodiac Killer, and Jeffrey Dahmer, and witnesses the guests murdering a man who has been picked up by Sally. After passing out during the dinner, John wakes up in a now empty room where the dinner was held with only Sally in it, who asks him if he knows what is and isn't real anymore.
John Lowe tells his lieutenant about the "copycat" serial killers at the hotel on Devil's Night, knowing how insane he sounds. John's reputation has been in tatters since his breakdown following Holden's abduction, and he is fired for instability. John awakens again, this time scratched and in bed with Sally. She claims he practically dragged her into his room from the bar, where they had sex. He says she needs to go, and she recoils after their evening together. He claims he doesn't remember any of it, and she says he's lying; she also thinks it is their destiny to do it again and again, and that he can't fight it.
Although he was sacked, John won't stop looking for answers about the Ten Commandments Killer. He checks into the West Los Angeles Health Center on purpose after finding out that someone related to the murders is kept there. After beating up the guard, he walks into the ward and finds Wren, one of the Countess' blood-sucking children. They have a small talk and she decides to lead him to the killer if he takes her out of this place. They leave the hospital unnoticed but Wren says that the murderer is at the Cortez and commits a suicide.
He goes back there and tries to make Liz Taylor tell him something. Then Sally appears and asks him to follow her in order to find out who the killer is. She leads him to Room 64 where she shows him a secret room with inwards of all the victims (even some who were killed in the 1920s) and tells him that James March was the one who started it but John himself finished his business unconsciously. It turns out that John has visited the hotel for the first time far back in 2010 while being drunk (see more on Background). He went to the police and confessed to his friend Detective Hahn but he wouldn't believe him and tries to convince him that he is a good person. Then, John says that he knows that Andy and Alex have been dating and stabs him to death. He returns to the Cortez and meets Iris. She tries to act as if she sees him for the first time but John tells her that he remembers everything and he goes to Room 64. He puts a part of Andy in one of the tubes left for parts of the victims killed because of the Ten Commandments.
It is revealed in The Ten Commandments Killer that John has been in a mostly sexual relationship with Sally, for five years, and yet he couldn't recall most of them until recently. John does not love Sally, and often neglects her, and ignores her, to be with his wife, Alex, whom he has strong feelings for. Sally loves him, and he cannot return the feelings he has for her, for the sake of Alex, Scarlett, Holden, and his personal well-being. The fate of John and Sally's relationship has yet to be determined. He later gets killed by the LA Swat team which is similar to Tate Langdon's death. His spirit later communicates with Billie Dean Howard on Devil's Night in 2022. 
- John: "He's saying "Get me out of her". He's still inside of her. You're going to find male potency drugs in his system...probably a lot. You won't be able to detach them here so you're going to have to take him with the corpse."
- John Lowe
I can't help but wonder how come..
- Hypodermic Sally
How come a girl like me ends up with tracks in her arms living in this dump?
- To Alex: "Do you ever hope?"
- To Sally
What we have is an Addict's High. In the moment it seems like it's never-ending, but it always ends.
- John: "I'm a homicide detective. What I know is that death is the only thing in life that has any meaning."
- To James March
I once walked in on a 273D, domestic dispute in progress. It took everything I had not to.. pound this guy's face, make him swallow his own teeth and blood. If it was up to me? I don't need a judge to tell me whether someone's guilty or not, I know. If they took the leash of me, crime would truly drop in this city.
- John Lowe is the second character portrayed by Wes Bentley. For a complete list of his characters, see Cast.