Arc Villain / Criminal Case

By nature of the mystery element of the game, spoilers will be unmarked.

Grimsborough

• Industrial Area: A Big Bad Ensemble between Tony Marconi, boss of the Italian mafia, Troy Cassidy, leader of The Skulls gang, and Salvador Cordero, leader of The Vipers gang, with each one causing havoc in their own way, including against each other.
• Financial Center: Alden Greene, a Corrupt Corporate Executive whose company Greene Holdings has a stranglehold on the district. In the district's finale, you also learn he's financing a Super-Soldier project that turns people into killing machines.
• Historical Center: Margaret Littlewood, a Glory Hound old lady who has been poisoning dogs so her own can win the Dog Pageant Contest. In the district's finale, she also kills one of the owners and attempts to do the same with Jones.
• University: The Rorschach Reaper AKA Tess Goodwin, a Serial Killer who hypnotizes students into killing their friends or relatives they hold a grudge against.
• Maple Heights: At first, it appears to be that Adam Bentley has been behind some of the murders happening across the district in his efforts to become richer and powerful, but he's killed by Chief King in the district's finale without any explanation as of why before he commits suicide. Then in the game's final case, it's revealed that the true villains of the district were Howard and Serena Johnson, members of the Crimson Order who ordered Chief King to assassinate Adam after he tried to blackmail them for some of the Crimson Order's gold.
• Airport: Milton Grimmes, the leader of the Ancient Conspiracy known as the Crimson Order that has been controlling Grimsborough from the shadows for centuries, effectively making him the Big Bad of the season. His ancestor, Solomon Grimmes, also serves as the main villain of the flashback segments found in each case, being the original founder of the Crimson Order and the one who killed all of the Aloki people to steal their gold.

Pacific Bay

• Ocean Shore: Whilst not actively threatening or plotting anything beyond having a good life, Derek Stone serves as the main antagonist of the district, being a thief and drug dealer who Frank has been trying to lock behind bars for a long time.
• Bayou Bleu: Erikah Mabayo, a woman posing as a supreme Witch Doctor who has started a voodoo craze within the district so she can scare people into submission with her Fake Wizardry. In The Climax, it's also revealed that she's a Serial Killer who has been murdering prostitutes working under her whenever they try to escape from her clutches.
• Inner City: A Big Bad Ensemble of no less than five antagonists. First there's Nikolai Kamarov and Sue Xiong, leaders of the Russian and Chinese communities, respectively, who serve as the main source of conflict for the community feud. Then there's Fredo Mancini, leader of the anarchy group known as Inner Chaos who is trying to plunge the streets into chaos by intensifying said feud with its propaganda. And finally we have Mark McKenzie, a Back-Alley Doctor responsible for stealing organs among various of the district's victims, being paid by The Man Behind the Man Rupert Snow to do so.
• Jazz Town: A Big Bad Ensemble between Veronica Blade and Freddie Alonzo. The former is the one responsible for stealing the army's weather machine and using it to create two hurricanes in an attempt to destroy Jazz Town, and the latter is the true identity of The Puppeteer, a Serial Killer who has terrorized the district for decades.
• White Peaks: The Night Walker, a Slenderman-esque boogeyman who lives in the forest and has been kidnapping people away for some time. In the end, the Night Walker turns out to be none other than Duncan Young, Amy's own brother.
• Ivywood Hills: Holly Hopper, leader of the religious cult known as the Utopians that serve as the main source of conflict during the district.
• Rhine Canyon: General Freeman, an army general who indulges into Fantastic Racism towards aliens and wants them to be exterminated to hide their existence from the public.
• Innovation Valley: Aphro-Dyte, a Killer Robot behind the machine uprising in the district who also tries to annihilate all humans with nanobots during the finale.
• Paradise City: Karen Knight, being the one behind the casino heist plan so she could steal the plutonium stored inside of its vault. For his part, Louis De Rico serves as The Heavy after appearing to be the main antagonist for a big portion of the district, since he was taking orders from Karen about putting together a Caper Crew.
• The Wastes: Albert Tesla, a Mad Scientist who has uploaded his mind onto a computer to survive forever and is revealed to be The Man Behind the Man of all the wrong things that have been happening in Pacific Bay, making him the Big Bad of the season.

World Edition

• Europe: Archibald Gilchrist, leader of the cult known as the Promethians which serve as the main source of conflict during the storyline. In addition, he's later revealed to also be part of SOMBRA, managing the Promethian cult as the organization's European branch.
• Sahara Region: The Sword AKA Omar Bahir, a SOMBRA assassin responsible for murdering Chief Ripley who is now spreading extremist ideologies all over the Sahara so people will become rebels and lead an uprising towards foreigners and people in power.
• Eurasia: Natasha Romanova, the head of COSMORUS who also happens to be The Mole that has been helping SOMBRA build their satellite, all for the sake of receiving total control over Russia if she complied.
• South Asia: Warren Goodfellow, a SOMBRA agent who has been posing as a NGO worker providing help for the disaster-afflicted parts of the region while stealing charity money and giving it to SOMBRA, all while framing the innocent guru Om Padmasana for his misdeeds by painting him as the one behind O.M. MediLab.
• East Asia: Both Ronin Ozawa and Obaasan serve as the main antagonists of the district, the former being "The Head Hunter" responsible for kidnapping and training children for SOMBRA all over the region and the latter the one in charge of Brainwashing and putting them into a Deadly Game so they can kill each other. Interestingly, they appear to be working independently of each other despite both of them being allied with SOMBRA, making them a Big Bad Ensemble instead of the expected Big Bad Duumvirate.
• Oceania: Professor Marshall Metcalf, a SOMBRA scientist in charge of "The Next Level" program whose sole purpose is creating brainwashed and genetically enhanced assassins for the organization.
• Africa: A Big Bad Duumvirate between Lavinia De Brills and Angela Douglas. The former is the one leading the diamond smuggling operation across Africa for SOMBRA, and the latter is the identity of the traitor inside the Bureau that keeps sabotaging the team's efforts while also being the one who recruited Lavinia for SOMBRA in the first place.
• South America: El Rey AKA Arsenio Castillo, the original leader and one of the founders of SOMBRA who decades ago started everything the Bureau has gone through the season and now has decided to step out of the shadow and make his presence known.
• North America: Hector Montoya, Arsenio Castillo's successor and the new El Rey who has been leading SOMBRA for the past decade while making them grow even stronger, making him the Big Bad of the season. For her part, Vice President Sarah Bennett serves as his Dragon and the one behind the rising political tensions between the United States and the Unified Nations, and becomes the Final Boss of the season after Hector's arrest in the penultimate case, conducting his plan of kidnapping the President of the United States to lead the country in a war against Russia and the rest of the world.

Mysteries of the Past

• New Haven: Edward Whimple, a corrupt police officer behind both the operation involving Irish immigrants being sold to rich people for cheap labor and the man-made fire that almost destroyed the entire district in an effort to dispose of the evidence incriminating him, all while using Father Donovan as The Scapegoat for his actions.
• Elysium Fields: Mr. Alastor AKA Archie Rochester, a young rich boy throwing fancy parties which, according to his complicated calculations, will result in the inevitable death of one of the guests at the hands of another, all with the purpose of courting a girl who has been tormented by the aforementioned victims in the past.
• Century Mile: Although Eleanor Halsted is exposed by the end of Century Mile as the saboteur that has been tampering with the World Exhibition's inventions, it turns out that she was only doing it because Stanley Spark was paying her to do so, intending to win the contest with foul play and therefore making him the true main antagonist of the district.
• Sinner's End: A Big Bad Duumvirate between the Flanagan siblings, Finley "Mad Dog" Flanagan and Fiona "The Viper" Flanagan, who serve as the leaders of the Irish mafia controlling the entire district with an iron fist. In addition, Fiona is also revealed to be the Scarlet Slayer, a Serial Killer murdering the prostitutes of Sinner's End and terrorizing the district, making it a strange case of a character serving as the main villain of two ongoing plots at the same time.
• Coyote Gorge: Vittorio Capecchi, the boss of the Italian mafia that has conquered the entirety of Coyote Gorge and is now forcing residents out of their homes so he can steal their lands and sell them for profit to a railroad company.
• Crimson Banks: Franca Capecchi, The Mafia's new boss who is hiding somewhere in the district while planning to start a Mob War and kill as many Irish people as possible to avenge her husband's murder.
• Wolf Street: A Big Bad Duumvirate between Larry Rochester and Deputy Mayor Sandra Hwang; the former is the true mastermind behind a big con created to scam people out of their money by investing on a fake telephone company with promises of saving them from bankruptcy, and the latter is the Corrupt Politician who has been aiding him by diverting attention away from his family and their illicit activities.
• Grim Chapel: A Big Bad Duumvirate between William Oland and Sylvia May, an Outlaw Couple aiding rich people (such as the Rochesters) dispose of their enemies though their own different means: while William poses as "The Devil" and helps them commit murders by disguising them as supernatural occurrences, Sylvia uses her position as a nurse at Gryphon Sanctuary to wrongfully commit sane people that are seen as a threat by the family, taking them out of the picture through non-violent means.
• Ivory Hill: A Big Bad Duumvirate between Senator Malcolm Rochester, the one pushing the bill to abolish freedom of press in all of Concordia except for the Rochesters, and his uncle Horatio, who is planning to Take Over the City once said bill is put into motion with the Rochester family at the helm of the New Concordia, all with the help of Commissioner Thaddeus Mulroney in charge of providing them with police support and authorize the release of Eleanor Halsted to assassinate their political enemies. In the penultimate case of the district, it's also revealed that Horatio was the one behind Vittorio's actions back in Coyote Gorge and, by extension, the Mob War between the Irish and the Italians in Crimson Banks, as well as the one making use of The Devil and Gryphon Sanctuary's false commitments in Grim Chapel, effectively making him the overall Big Bad of the season.
• Capitol Peak: Mayor Justin Lawson, who undergoes a Big Bad Slippage by turning into a ruthless dictator after witnessing first-handed the consequences of unrepentant police corruption, violent Mob Wars, and the Rochester family fueling all of these problems for their own gain over the course of the storyline, becoming the Final Boss of the season with the defeat of the aforementioned Big Bad Shuffle.

The Conspiracy

• Fairview: The Rocket Cow Killer AKA Rosamund Wilcox, a Serial Killer targeting parents who've had a fight with children attending the high school where she serves as the principal, seeing herself as their savior no matter how much trauma she causes to them.
• Money Mile: A Big Bad Ensemble between Meera Kat and Christian Bateman. While neither of them are responsible for either the disaster that has struck Money Mile or Zoe's disappearance, both of them still end up being the two most troublesome people encountered during the district, as Meera has been taking advantage of the destruction, grief, and suffering brought by the earthquake to advance her career by creating art pieces out of them without caring about what the traumatized victims might think, while Bateman is revealed to be a psychopathic time bomb with a strong sense of entitlement to do whatever he pleases just because of his wealth, leading to murdering Meera himself after she refuses his advances on her.
• The Greens: Rozetta Pierre is an Implied example during the district's duration. While she's the founder of DreamLife and the creator of a new VR game that has been getting people dangerously addicted to it, the district ends with her true involvement being left entirely ambiguous when not only she excuses herself claiming that the addiction-inducing "bug" wasn't officially authorized and the responsible party has already been fired, but also provides you with the means of getting its victims back to normal without asking for anything in return. As such, The Greens is left with no established antagonist until Rozetta's evilness and direct involvement with the bug are properly revealed in the Misty Grove district.
• Old Town: While Steven Crowe is initially hyped as the main antagonist of Old Town due to being the leader of The Higher Truth, it's his second-in-command Grayson Rosewater who is exposed by the end of the district as the true mastermind behind the cult being a Scam Religion designed to strip people out of their money, as he's revealed to be working for DreamLife, the ones receiving all the cult's profits to keep funding their company.
• Maple Heights: Dr. Ernest Emerson, a scientist who, in an effort to prove that prehistoric creatures are capable of suddenly returning to the modern world, unleashed the deadly Demon Fish into the Grimsborough river by blowing a hole in their cave, not caring about the consequences of freeing a potentially dangerous species into the city water supply and leading to the deaths of dozens.
• Misty Grove: Rozetta Pierre, who over the course of the district is exposed as the Big Bad of the season when the unethical and outright illegal experiments she's been conducting under DreamLife's dome are slowly unraveled when the police department infiltrates it, not to mention the reveal that the mind-controlling "bug" back in The Greens was completely intentional and her reckless experimentation also provoked the earthquake that destroyed Grimsborough.
• University: A Big Bad Duumvirate between Dorothy Kix, Polly O'Brien, Courtney Guerra, Lucius Roth, and Azeeb Patel, the new generation of the Covert Group known as Ad Astra which Rozetta Pierre founded years ago in an effort to create an elite capable of controlling the rest of the population. In The Climax, it's revealed that Rozetta has been giving them orders from prison to carry on her legacy, which ends with the five of them murdering a professor aware of the identities of the original members of Ad Astra.
• Spring Fields: A Big Bad Duumvirate between Julia Brine, Christian Bateman, and Mayor Joe Warren, three of the five original members of Ad Astra who are revealed to still be working with Rozetta Pierre, with Julia burning the corn fields of Grimsborough to create new ones infused with DreamLife's mind-altering drug and Bateman and Warren setting up an Assassination Attempt on the player that ends in the death of a member of the police force.
• Airport: Louis Leroux, the final member of the original Ad Astra who is revealed to be a false ally using his job as a reporter and informant to provide false information to hide Ad Astra's schemes, and ends up murdering Jones' girlfriend when she refuses to cooperate with him regarding the experimentation that was done to her under DreamLife's dome. However, he gets Hijacked by Ganon in The Climax when the Greater-Scope Villain of the season and true leader of Ad Astra orders his death after finding no more use for him or the rest of the group.
• Newmark: Denise Daniels, Rozetta Pierre's mother and Ad Astra's true leader who is exposed as the true mastermind behind DreamLife and Ad Astra's actions in an effort to create a superhuman species for her to control. However, she ends getting usurped by her assistant Otto Kessel in the game's finale, who becomes the Final Boss of the season after murdering Denise to take control of her superhuman army after being revealed to be one himself.

Travel in Time

• Ancient Times: Great Consul Octavian, who is planning to burn Egypt to the ground so he can keep power over the Roman Republic.
• The 1960s: Congressman Graham Winslow, who kills Soviet Ambassador Lev Romanov in the district's finale so the United States and the Soviet Union go from a Cold War to a nuclear one.
• Renaissance: Cardinal Cisneros, leader of The Spanish Inquisition and the one responsible for incarcerating Leonardo da Vinci in the first place.
• Altered Present: The Ptolemy Dynasty - led by Pharaoh Ramses XLIII and Queen Shabaka - responsible for altering the timeline to make Egypt a global superpower. Particularly, Nebet is revealed to really be Princess Nefertiti, daughter of the Ptolemian leaders, who had been helping Ammon Bast and disguised herself as a Fish out of Temporal Water to spy on the team.
• Age of Sail: Ammon Bast, the main lackey of the Ptolemy Dynasty and saboteur of the Time Machine who is now trying to stop the team from fixing the altered timeline.
• Medieval Asia: Ogedei Khan, who is planning to destroy China with weapons brought from the future by Ammon Bast.
• The End: Nefertiti and Ammon.

Supernatural Investigations

• West: Eric Zwart, the vampire responsible for :kidnapping Mina Reynolds in an effort to create an invincibility elixir.
• Southwest: Abigail Riley, the ghost of a woman sacrificed five years ago who has been possessing people so they commit murder. Her sacrifice also ended up summoning Zeke Davis, the villain of the next region.
• The Rockies: Zeke Davis, the demon summoned five years ago who has been draining the life of livestock over the Southwest and is trying to steal the core of a magical tree that serves as one of the keys for the Demon Queen's cage.
• Midwest: Morgana Blackhawk, the witch who has been kidnapping children over the region so she and her coven can eat them for power. She then returns two regions later, killing Gwen's mother in exchange for demonic powers after an alliance with the Demon Queen.
• East: Reggie Pratt, the demon searching for the final key for the Demon Queen's cage. In addition, he's also revealed to be the demon who mentally tortured Gwen in the previous region.
• South: The Demon Queen under the guise of Chief Arrow's wife, Lily Arrow, who also serves as the Big Bad of the season and is planning to destroy the world with an army of demons.

City of Romance

• Fantasy: No main villain, as the arc focuses on finding Carrie's brother.
• Attraction: Antoine Macaron, the ringleader of the animal smuggling ring.
• Obsession: Melodie Laurence, the creator of the hearts feature on Luvver which people obsess over and match them with incompatible people.
• Jealousy, Separation, and Engagement: Eleonora Macaron, who turns out to be Evil All Along and was working with Samy and Antoine in a scheme to make the latter president of France.