In 1968, demonologists Ed and Lorraine Warren take custody of the possessed Annabelle doll from nursing students Debbie and Camilla. While driving home, their car breaks down beside a foggy cemetery, where the doll summons wandering spirits to attack Ed before they manage to escape. At their house, the Warrens place the doll inside a sacred glass cabinet in their occult artifact room, sealed with wood from a church altar and blessed by Father Gordon to bind the demonic evil.
In 1972, Ed and Lorraine depart on an overnight case, leaving their ten-year-old daughter Judy in the care of babysitter Mary Ellen. Judy struggles with isolation at school, as classmates bully her after local newspapers publish sensational stories about her parents' investigations. Mary Ellen's lively best friend Daniela Rios drops by uninvited, bringing birthday gifts for Judy. Daniela harbors a secret agenda: her father recently died in a car crash for which she blames herself, and she hopes the Warrens' supernatural artifacts can help her contact his spirit.
While Mary Ellen and Judy are outside roller-skating, Daniela sneaks down into the locked artifact room. Fascinated and desperate, she touches various cursed objects, including a mourning bracelet, the piano, and the Samurai armor. Drawn to the glass case, Daniela uses the key to open Annabelle's cabinet, leaving the door unlocked when she gets spooked. The entity inside the doll awakens, acting as a spiritual battery that supercharges every cursed artifact in the room.
That night, the house turns into a supernatural battleground. The Ferryman hunts Mary Ellen with coins covering corpses' eyes, a bloody wedding dress possesses Daniela, a spectral werewolf stalks Mary Ellen's crush Bob outside in the backyard, and Annabelle stalks Judy in her bedroom. Judy realizes that Annabelle is not just a monster, but a demonic beacon orchestrating the entire assault to harvest a mortal soul.
Realizing that sealing the doll is the only way to silence the other spirits, the three girls brave the haunted rooms to find Annabelle and return her to the glass case. Judy uses her mother's rosary and a recorded reel of Father Gordon's exorcism rituals to weaken the demons, while Mary Ellen and Daniela retrieve the doll from the demon's clutches. Together, they force Annabelle back into the glass cabinet and lock the door, immediately banishing all the roaming spirits back into dormancy.