Isaac wakes up with amnesia but is rescued from the Alpha pack by a mystery girl. Jackson has moved to London. Allison and her father have quit being werewolf hunters, and Scott is working on being a better person. Derek has been looking for Boyd and Erica, who were captured by the Alpha pack. Something eerie is causing the animals of Beacon Hills to go insane, and Dr. Deaton concludes that the animals are killing themselves intentionally. Derek gives Scott the tattoo he has been wanting to get, and explains about the Alpha pack's leader Deucalion, who is blind but the strongest and most lethal.
Stiles' childhood friend, Heather, is attacked and goes missing. The guys help Isaac recover his memory, and it is revealed that he had found Boyd and another female werewolf, being kept in an abandoned bank vault. However, Erica may already have been killed. When Derek and Scott break in to save them, Derek recognizes the other female werewolf to be his little sister Cora, previously thought dead. Stiles and Peter discover that Boyd and Cora have been kept from transforming for 3 months. Wild and bloodthirsty, Boyd and Cora almost kill Derek and Scott until Allison saves them by setting the wolves free.
Scott reveals to Allison that her mother tried to kill him, while Derek discovers Erica's body. Derek, Isaac, and Scott seek help from Chris to capture Boyd and Cora before they kill someone. Lydia finds a dead boy, and calls Stiles for help. The guys trap Boyd and Cora in the high school's boiler room but discover Jennifer is inside; Derek saves her. Stiles discovers Heather's body in the morgue, killed the same way the boy was. As the two were both virgins, Stiles concludes that someone is murdering them to offer as human sacrifices, just as Sheriff Stilinski discovers a third dead girl, killed the same way.
The body of the newest murder victim is found. The Alphas attack Derek, and Deucalion offers him a proposition: join the Alpha Pack by killing his own Betas and absorbing their power. Stiles, Lydia and Deaton figure out that the serial killer is a Darach, a dark or evil druid. Mr. Harris is murdered next, though he seemed to know the killer. Derek, aware Deucalion wants him to kill his pack, kicks Isaac out, so Isaac moves in with Scott.
The Beacon Hills cross-country team is heading to a cross-country meet aboard a bus, which Allison and Lydia are following to keep an eye on Scott. Scott is suffering from a nasty injury that isn't healing; a result of a preemptive strike on the Alphas the night before. The battle leaves everyone under the impression that Derek is dead, which Scott feels responsible for. The Alphas take a wounded Ennis to Deaton in hopes to heal him. However, Deucalion kills Ennis and absorbs his power. Allison stitches up Scott's wound, allowing him to finally heal. Back in Beacon Hills, Jennifer is startled when a wounded Derek appears and passes out.
The team takes refuge at an eerie motel for the night, where Scott and the gang undergo strange experiences. Boyd, Ethan, and Scott suffer various types of hallucinations that drive them to attempting suicide while Isaac is triggered into a PTSD flashback. All four werewolves are saved by Stiles and Lydia. Lydia realizes that the Darach caused this to happen, intending to use the wolves as sacrifices. Meanwhile, Jennifer helps to heal Derek when the two have sex. Chris visits a wheelchair-bound Gerard in regards to his uncle, who committed suicide in 1977, wanting to know which Alpha had bitten him. Gerard reveals that it was Deucalion.
The Darach targets Deaton as the next sacrifice, leaving him hanging by his wrists to die. The Alpha Pack attacks Derek while Scott saves Deaton, with the help of Sheriff Stilinski. Deaton reveals Scott is a "True Alpha": a werewolf who rises to Alpha status purely by their own willpower and good character. This is extremely rare, happening every 100 years, which is why Deucalion is after Scott. Kali forces Derek to kill Boyd, which also reveals Erica's death to him, and causes Derek to break down.
Seeking answers, Scott, Allison, Stiles and Cora hear stories told by two unlikely narrators (Peter and Gerard) and discover a secret about the color of a werewolf's eyes, that they change from yellow to blue when an innocent life is taken. The tale told by Peter focuses on Derek when he was a teenager. It is revealed that Derek fell in love with a girl named Paige, who he was forced to kill in order to end her suffering from a bite from an Alpha werewolf (Ennis); killing Paige darkened his soul and changed the color of his eyes. The tale told by Gerard explores the origins of the feud between the Hunters and the Packs, and it is revealed that Gerard was the one who blinded Deucalion, who was seeking peace with Gerard, during a meeting between the two sides. Also, Dr. Deaton and Ms. Morrell are revealed to be emissaries, or modern day druids, the ambassadors between the Packs and the rest of humanity.
Allison and Isaac learn that the Darach is planning to sacrifice guardians next, they think that her father is involved with the murders, but end up discovering that he has been tracking the Darach for a while now. Meanwhile, Scott and Stiles want to use Lydia to solve the murders. Lydia discovers that Jennifer Blake is the Darach; Jennifer is about to kill her, when Lydia screams and she realizes that Lydia is actually a banshee, aka "the Wailing Woman"; this explains her attraction and inclination towards the supernatural. Stiles' dad tries to save Lydia, but is kidnapped by Jennifer, as he is a guardian. Scott goes to Ms. Morrell for some guidance; Morrell reveals that Deucalion's plan for him is that either Scott will join the Alpha Pack willingly as a True Alpha, or Deucalion will force Scott to kill, destroying his potential to become a True Alpha.
After Jennifer takes Stiles' dad, Derek and Scott capture her and bring her to the hospital in order to save Cora's life, where they are trapped by the Alphas. It is then revealed that Jennifer is in fact Kali's former emissary and that the Alphas want her dead. With the help of Peter, Allison, Chris, Stiles, and Isaac, they manage to fight against the Alphas and escape, but Jennifer kidnaps Scott's mom, since she is a guardian. Feeling that there is no other way, Scott joins Deucalion to find Jennifer, who promises to help find his mother and Stiles's father in return.
After escaping the Alphas, Derek and Peter try to find a way to save Cora, while Allison, Isaac, and Stiles discover that Jennifer has named Chris Argent as her last sacrifice. Sacrificing himself to save Allison, Chris hands himself over to Jennifer. The group discover that Jennifer is holding her victims in the root cellar. Scott and the Alpha pack hunt down Ms. Morrell; Deucalion injures her with the blade in his cane. Peter tells Derek that as an Alpha, he can heal one of his own, even at the brink of death. Choosing family over power, Derek heals Cora, losing his Alpha powers in the process. Stiles and Deaton find Scott and convince him that they need to be 'temporarily' dead in order to find out where their parents are. Scott, Allison, and Stiles are then put into tubs of ice and pushed down.
Scott, Allison, and Stiles awaken and discover where the Nemeton is located. Jennifer kills Kali and badly wounds the twins. Allison, Isaac, and Stiles locate the Nemeton and rescue the three parents. The lunar eclipse begins, and all the werewolves become powerless. Jennifer gives Deucalion his sight back so he can see her true form and then tries to kill him, but is stopped by Derek. Jennifer attacks Derek, but the eclipse ends and the werewolves' power returns. Scott defeats Jennifer and becomes a True Alpha. Deucalion slashes Jennifer's throat, apparently killing her. Jennifer is revealed to be barely alive, having survived Deucalion's attack, but is confronted by Peter. Peter kills her, claiming that he has always been the Alpha.
As a result of their "temporary deaths", Scott, Stiles, and Allison are now experiencing vivid hallucinations. Allison is haunted by visions of Kate, her dead aunt; Stiles has terrible nightmares and is unable to read even when awake; and Scott has begun to see his shadow as that of an Alpha werewolf. Scott befriends a new student named Kira Yukimura, whose father has become the new history teacher at Beacon Hills High School. Overhearing a discussion involving the recent psychological problems that Scott, Stiles and Allison have been having, Kira identifies the condition as a spiritual state known as Bardo, the final stage of which ends in the death of the person afflicted. Scott and Stiles search a crime scene of the reopened case for clues, finding a coyote whose eyes glow blue. Scott believes the coyote is one of the family members presumed dead, a girl named Malia.
Scott and his friends attempt to track down the were-coyote Malia before her father kills her, in order to change her back to a human. Isaac becomes caught in a coyote trap, while Stiles saves Lydia from another trap. Allison uses a tranquillizer dart to sedate Malia's father. Scott tracks down Malia and embraces his Alpha powers in order to transform Malia back into a human with an Alpha roar, which also gives Isaac the strength to break the trap on his leg. Sheriff Stilinski then reunites Malia with her father. Stiles discovers that he has regained the ability to read. Meanwhile, Peter and Derek are freed from their captors by an unlikely ally, Braeden, who reveals that she was hired to free them by Deucalion. At the Nemeton, someone releases a swarm of fireflies that morph into three mysterious figures.
William Barrow, an electrical engineer turned mass murderer, escapes during a surgery at the hospital and hides out in the school. He abducts Kira, takes her to a power plant and attempts to electrocute her, but she inexplicably deflects the electricity, killing Barrow and shutting down the power for the entire town. Just after the blackout, five hooded figures attack Isaac.
Isaac describes the hooded figures that attacked him to Allison and her father. Kira reveals to Scott that her body emanates a glowing aura when a photo is taken of her, and with the help of Stiles, the two break into the Sheriff's office and erase similar photos from Kira's cell phone. Danny and Ethan throw a Halloween party in Derek's empty loft. During the party, Scott realizes that Kira's "aura" resembles a fox, and Allison discovers what appears to be a reverse number "5" mark behind Isaac's ear. Ethan and Lydia are also attacked by the hooded figures and marked the same way. Stiles discovers that his handwriting matches the coded message written on the chalk-board, instructing Barrow to kill Kira.
Allison's father recounts his time in Japan when he was eighteen; he and members of the Japanese yakuza encountered the hooded figures, which are revealed to be called Oni. He, Allison and Isaac plan to infiltrate the lair of the only other survivor, a man called Katashi in order to gain answers. Worrying about his sanity, Stiles seeks help from Melissa. She discovers that his symptoms are identical to those of his deceased mother, Claudia. Scott, Kira, Derek, the twins, Melissa, and Agent McCall take sanctuary in Scott's home just before the Oni attack. The Oni are forced out of the house. Katashi warns Chris to let the Oni destroy the Nogitsune. The Oni breach Scott's house, but do not harm him or Kira. Stiles awakens and is confronted by the Oni, but he destroys one of them.
Stiles makes a panicked late-night phone call to Scott after he finds himself in a strange location with his leg in a steel trap. Lydia leads them to the mental health center where Barrow was committed, however Stiles is not there. Scott's mother and father find Stiles, who had been sleepwalking. Derek and Kira find Stiles's baseball bat at the power station, and Derek deduces that Kira was indirectly responsible for the Nogitsune taking over Stiles's body. Stiles has an MRI scan to test for frontotemporal dementia, the same illness that caused his mother's death. The power then goes out, due to the Nogitsune having damaged the wiring on the roof the previous night. The Nogitsune, now in complete control of Stiles's body, confronts the remaining Oni, who are revealed to be led by Kira's mother.
Deaton retrieves a poisonous plant that will aid him in defeating the Nogitsune. Derek and Chris Argent are arrested by Agent McCall for the murder of Katashi after being framed by someone. Stiles, who is still missing, reappears in the school basement. After finding a map of the cross-country trails, he, Scott, Aiden and Ethan realize that the path has been booby trapped by Stiles. The boys are successful in stopping the runners from being injured but Coach Finstock is shot with an arrow. Allison and Lydia seek the aid of Peter Hale. He asks for Lydia's help in finding the memory that his sister took away from him. Lydia discovers that Peter is a father. The Oni, attack Stiles, Scott and Kira at the vet's office. They manage to escape but Stiles - still possessed by the Nogitsune - knocks Kira unconscious.
Stiles checks himself into Eichen House, a mental hospital. Chris Argent and Deaton are working together. Deaton requires a hidden scroll in his quest to cure Stiles. In the mental hospital, Stiles encounters Malia Tate, who isn't pleased to be reunited. After group therapy, Stiles is told that he must stay awake. Stiles enlists Malia in a plan to access the basement. Malia rescues Stiles and the two head to the basement together, where they share a passionate encounter. Soon after, Malia realizes that the wall with the kanji carved into it is hollow, and the Nogitsune lies behind it. The Nogitsune gives Stiles an ultimatum; allow it in or watch Malia die, and allows the Nogitsune to possess him again. Deaton reads the scroll and says that the Nogitsune's host body needs to change its form in order to remove it.
Kira learns that her mother is actually a Kitsune who is close to 900 years old. During the second world war, she was in a Japanese internment camp, and fell in love with a young medic. A riot breaks out, and the medic is badly burned by a molotov cocktail thrown. Noshiko, assumed to be dead but actually healing and unable to move, calls upon a Nogitsune to possess her so that she can have her revenge, but it possesses her lover's body instead. Kira, as a Thunder Kitsune, is able to mend the broken katana, and her mother gives it to her to stop the Nogitsune once again. Noshiko reveals that she hid the Nogitsune in the roots of the nemeton, meaning that Scott and his friends may have been responsible for the reawakening of the Nogitsune. Derek, Chris, Allison and Sheriff Stilinski try to track down Stiles, hoping to bring him back to normal.
Sheriff Stilinski faces a review board, but Scott's father saves his job at the last minute. Mr. McCall reveals to Sheriff Stilinski that he only came back to Beacon Hills to make amends with his son. Meanwhile, the Nogitsune stabs himself and releases a swarm of flies, sending them after Aiden, Ethan, Isaac and Derek. Having been placed under the spell of the Nogitsune, Derek tries to get revenge over Chris, by covering him in gasoline and attempting to burn him; however Chris is able to free himself. Aiden, Ethan, and Isaac nearly kill each other but are saved by Kira and Allison. With guidance from Peter, Scott and Lydia are able to enter Stiles's mind, and manage to free Stiles from the Nogitsune's control. However, Lydia is kidnapped by the Nogitsune, which is now independent and looks exactly like Stiles.
While searching for Lydia in the woods, Aiden and Ethan are shot at by an unknown shooter with wolfsbane bullets, and are saved by Derek. Kira's mother tries to teach her the board game that Stiles was playing with the Nogitsune. Later, Kira's father discovers that the Nogitsune and Kira's mother play the game the same way. Lydia is taken to the internment camp by the Nogitsune; the group arrive and find Kira's mother and the Oni, who plans to kill the Nogitsune. The Nogitsune takes possession over the Oni and has them face off against Kira, Allison, and Isaac, while Scott and Stiles find Lydia and are shocked when she asks why they came when she told them not to. Allison manages to kill one of the Oni and is stabbed by another. Allison professes her love to Scott and dies in his arms.
The Oni, under the control of the Nogitsune, systematically and violently take control of the hospital, Sheriff's station, high school and Alan's animal clinic. Isaac and Mr. Argent realize that silver can actually destroy the Oni. Everyone shows signs of the poisoning seen in others attacked by the Oni. But Scott, Kira, Stiles and Lydia defeat the Nogitsune by realizing the attacks are an illusion. Scott bites the Nogitsune, following the instructions on the scroll stating that it cannot be both a fox and a wolf. The duplicate of Stiles that the Nogitsune was using as a body disintegrates, and Isaac traps the Nogitsune in a box made of Nemeton wood. Lydia then gets a feeling and runs outside to find that Aiden has been stabbed and now is lying dead in the arms of Ethan, his twin brother. Later, the injured people start healing and all seems well again in Beacon Hills. In a series of flashbacks, it is revealed that Kate Argent, whose throat was torn out by Peter's claws, is shown to be alive and is a supernatural being.