Marion Chambers Whittington returns home from work to discover her house broken into. She seeks help next-door, where she runs into the teenaged Jimmy and his friend after a game of hockey. They take her inside, where she calls the police for back-up; Jimmy, however, decides that he can investigate Marion’s house by himself. The office is the only room that’s been ransacked, and with Jimmy determining the coast to be clear, Marion makes her way back inside.
She soon realizes that her file on Laurie Strode has been emptied out, and she may not be alone in her house either. She makes her way back next door, only to discover the two teenagers murdered and herself now trapped inside Michael. The police arrive at her house, but before she can signal for help, Michael kills Marion as well and steals her car.
After faking her death, Laurie Strode is now known as Keri Tate, the high-strung headmistress of a small private prep school in California. Still recovering from the events of that fateful night twenty years ago, Laurie has turned into a functioning alcoholic (in the words of her teenage son, John) and has a dependency on her prescription pills to help keep the nightmares away. The of them live on campus, along with several other students at the school. Laurie has a secretary named Norma who dotes on her like a parent, and has taken a notice on how Laurie gets particularly shaken around Halloween. Laurie’s boyfriend Will Brennan is the campus’ guidance counsellor, but the two of them have to keep their relationship a secret at Laurie’s insistence.
Laurie’s relationship with the seventeen-year-old John is becoming strained. As the result of her past, she is overprotective of him and keeps him locked within the locked school grounds at all times. Despite John’s complaints, Laurie denies him the opportunity to attend an annual school camping trip to Yosemite, which leaves on Halloween. John’s girlfriend Molly also stays behind due to some problems with her tuition, leading to their friends Charlie and Sara to fabricate their own reasons to stay behind so that the four of them can celebrate Halloween together on the near-deserted campus.
With the plan set in stone, John and Charlie manage to convince Ronny, the school’s security guard, to open the gate for them to make their way to the city to shoplift some alcohol for the night. Unbeknownst to them, Laurie and Will have plans for lunch in town as well. During their lunch, Laurie attempts to open up to Will a little, acknowledging that she’s been unable to deal with something in her past. When he leaves her alone momentarily, Laurie quickly consumes her first glass of wine and orders a second glass to help calm her nerves. On her way back to the school, Laurie sees John and Charlie walking down the street and becomes enraged that John has left the school grounds against her orders. The two quickly get into an argument in the street, ending with John chiding Laurie that he’s old enough to make his own decisions and that Michael Myers has been dead for twenty years.
Michael Myers, however, has finally made his way to the school grounds and waits for the night to fall.
With one final class before the students leave for Yosemite, Laurie reminds them of the school’s code of conduct and rules for the trip. Afterwards, she surprises John by telling him she’s changed her mind and she will allow him to go with the others. Having already made plans with his friends, John decides to stay behind anyway, but doesn’t tell his mom.
Once the busses leave for Yosemite, Michael makes his way to the campus. He distracts Ronny by the gate with his car and secretly sneaks in behind him when Ronnie is investigating. Inside, he quickly disposes of Charlie – who was hunting for a corkscrew – before brutally murdering Sara after she goes to investigate Charlie’s disappearance.
With Laurie and Will alone, the two bond some more and Laurie finally starts to reveal her past to Will. Though he initially thinks she’s joking, he quickly realizes how serious her statements are. When Laurie realizes that she and John are now both 17 on Halloween, panic sets in and she discovers that John never actually left for Yosemite like he said he was. It’s at this point Ronny arrives and informs her of the strange, deserted car by the front gates, and the three of them set out to hunt for the others.
Realizing their friends have been gone for a while, John and Molly go to investigate where they friends are and quickly discover Sarah’s body hanging from a light fixture in the kitchen. Michael Myers appears and begins to chase them, causing them to flee towards John’s residence. They lock a gate behind them, but Molly drops the keys outside of the gate, leading Michael to grab the keys and begin working on unlocking the gate.
Laurie and Will hear the commotion and let John and Molly in just as Michael unlocks the gate. Locking the door, Laurie and Michael make eye contact through the doorway, seeing each other for the first time in twenty years. Before Laurie can get her gun to shoot Michael, he disappears into the night once more.
Forcing John and Molly to hide, Will and Laurie investigate the hallways for Michael. A shadow approaches and Laurie fires, only to realize afterward she’s now shot Ronny in the head. Grieving over the thought of his death, Michael approaches from the shadows and kills Will by stabbing him in the back and severing his nerves. Laurie manages to get away just in time to hide, before knocking Michael out with a fire extinguisher moments later.
She grabs John and Molly from their hiding spot as Michael begins to chase after them, and the three of them barely manage to escape in a car. As they approach the gate, Laurie decides she needs to fight Michael once and for all, and tells John and Molly to drive off for help before returning to the school to finish Michael off by herself.
The two of them stalk one another in the corridors of the school hallways, making their way to the cafeteria where Laurie is hiding under tables. He begins to flip the tables as she plots an escape, and after chasing her down once more, Laurie stabs Michael repeatedly with a knife until he falls over the balcony onto one of the tables. Ronny surfaces, alive, and tells Laurie that Michael is dead before she can do more damage to him.
Help arrives at the school, where everyone who’s still alive is being tended for their wounds. Laurie sees them wheeling Michael into the coroner’s van, and she decides that she needs to kill Michael once and for all for the horrors to end. She steals the van and drives off with Michael in it, eventually seeing him come to in the back and escape from his body bag. Laurie slams on the breaks, sending Michael flying through the windshield. Laurie waits only for Michael to stand back up before she drives the van off a cliff and crushes Michael against a tree.
Having been thrown from the van, Laurie finds the fire axe and approaches Michael. She calls to him and he looks up at her, mute but seemingly asking her for help by reaching his hand hand. Laurie reaches out for him and their fingertips touch only briefly before she swings the axe and decapitates Michael, seemingly ending her horror once and for all.