Lydia vanishes from the hospital after a disturbing hallucination, and is found naked in the woods two days later. Isaac, a tormented teen abused by his father, is attacked while working in his father's cemetery; Derek appears to save him. Jackson begins bleeding black blood and is told by Derek that his body is resisting the bite. Derek forces Scott to watch Gerard kill an innocent werewolf and declare that they will eliminate all werewolves to avenge his daughter Kate's death.
Isaac's father is murdered by a strange creature. Scott discovers Isaac is now a werewolf. Isaac is then taken into custody for his father's murder. When it is revealed that the werewolf hunters are going to kill Isaac, Scott, Stiles and Derek plan to save him, as he is innocent. At the jail, Isaac transforms and breaks out, advancing on Stiles. Derek, being the Alpha werewolf, is able to force him into submission. Jackson, who had set up a video camera overnight to record his transformation, is upset to learn that nothing happened.
Chris begins Allison's training to become a werewolf hunter. At school, Erica, an epileptic girl, has a seizure and ends up in the hospital. There, Derek delivers the bite upon the promise that her illness will vanish. Dr. Deaton finds a dead hunter in his office and Chris wants him to find out what happened. Scott discovers Boyd is now a werewolf and is forced into a fight with Derek, Erica, and Isaac. Jackson is shocked when he exhibits inhuman strength.
When Stiles takes his jeep in for repair, he is paralyzed by the creature's toxin and witnesses it kill the mechanic. Jackson discovers there are actually over 2 hours of missing footage from the night he recorded himself. The creature attacks Derek and paralyzes him. Derek falls into the pool and Stiles jumps in to save him. They discover the creature cannot swim, so they stay in the water until Scott saves them. Derek realizes that the creature is a Kanima. Gerard reveals he knows Scott's secret and blackmails him.
Convinced that Lydia is the Kanima, since she displayed immunity to the creature's toxin, Derek wants to kill her. Scott, Allison, Stiles and Jackson try to protect her together. After a fight with Derek's pack, it is revealed to everyone that Jackson is the Kanima.
Derek engages the Kanima in a fight interrupted by Chris and Gerard. The Kanima does not attack Gerard, instead seeming to communicate with him, which confuses Chris. After the Kanima paralyzes Danny and 6 others at a gay club, Jackson passes out, so Stiles locks him up in a police van. However, Jackson transforms and escapes. Allison discovers the Kanima seeks a master, revealing that Jackson is being controlled by someone.
A fight between Scott and Jackson lands everyone involved in detention. Jackson transforms, injures Matt and Erica, and leaves a warning from his master. Erica has a seizure as a result of the Kanima's venom and Scott and Stiles rush her to Derek. Lydia meets the strange boy she has been seeing around, only for him to reveal himself to be a younger version of Peter Hale. Lydia realizes that the young boy was a part of her imagination and that Peter has been communicating with her via hallucination all along
Jackson is commanded by his master to attend a secret rave, where his next target is. Stiles and Sheriff Stilinski realize there is a pattern in the murders: all victims had been in the class of 2006. Stiles's father loses his job because Stiles's irresponsible behavior reflects badly on the county. Scott is attacked by Victoria, who attempts to kill him. Isaac drugs Jackson, and he and Erica join Stiles in interrogating his master, who speaks through him. Jackson transforms, successfully killing his target. Derek saves Scott, biting Victoria in the process.
Stiles realizes that all the murder victims were on the Beacon Hills High swim team and the coach at the time was Isaac's father. At Lydia's birthday party, Lydia spikes the punchbowl with wolfsbane petals, causing all the party attendees to hallucinate the things they fear most. She attacks Derek and brings him to the Hale house, where Peter uses Derek's blood to come back to life. Victoria kills herself so that she would not become a werewolf. It is revealed that Matt is the Kanima's master.
Matt takes Scott, Stiles, Melissa and Sheriff Stilinski hostage. Gerard persuades Allison to exact revenge on Derek for bringing her mother to suicide. Matt reveals to Scott his reason for the murders: in 2006, all the victims were at a party at Isaac's house, where Matt had come to meet Isaac. They had thrown Matt in the pool and left him to drown despite him yelling that he can't swim. Melissa finally sees Scott as a werewolf. Gerard drowns Matt in the lake and becomes the Kanima's new master.
Boyd and Erica leave Derek, terrified of the Argent werewolf genocide. At the championship lacrosse game, Gerard threatens to murder someone with the Kanima if Scott does not bring Derek to him by the game's end. Allison ruthlessly shoots Boyd with arrows until the werewolves are saved by Chris, who is upset by Allison's actions. On the field, Stiles begins a massive winning streak, and their team wins. Just then, Jackson is found bleeding and unresponsive; he has stabbed himself with his own claws. Sheriff Stilinski makes a grim discovery: Stiles has gone missing.
Stiles is kidnapped by Gerard, who also has Boyd and Erica hostage; Stiles escapes. Chris, realizing that Gerard is the true enemy, sets Boyd and Erica free, and helps Scott and Isaac take Jackson's body to Derek. Jackson turns into the Kanima, and a battle ensues. Gerard reveals he has cancer and had planned to cure himself by becoming an Alpha werewolf. However, when Gerard's body rejects the bite, Scott reveals he had replaced Gerard's cancer pills with mountain ash. Jackson is killed by Peter and Derek but comes back to life as a blue-eyed werewolf. Allison tearfully breaks up with Scott, but he assures her he'll wait. Peter reveals a pack of Alpha werewolves have come to town, indicating new danger. This Alpha pack captures Boyd and Erica as they flee.