The story takes place in the year 1941. Elspeth "Doc" Holliday, a calm, collected research scientist, is dispatched to the town of Burkittsville by the Spookhouse, an fictional classified government agency charged with investigating paranormal occurrences.
It is reported that during the early 1940s a hermit named Rustin Parr abducted seven children from Burkittsville and, apparently without motive, murdered all but one in his basement. He forced the surviving child, Kyle Brody, to stand in a corner and listen to the screams of the children being tortured and killed. Afterwards Rustin Parr left his house in the forest, walked into town, and said to a local shopkeeper, "I'm finally finished." The player must guide Holliday through her investigations, to see if there is any truth to Parr's claims that he was under the influence of otherworldly forces when he committed the murders. The investigation includes conversing with inhabitants of the town and analysing clues. Action sequences occur intermittently in the woods where the legendary Blair Witch is rumored to live, as well as in nightmare sequences in which the inhabitants of the town seem to become Daemites (demonic zombies). The story of Rustin Parr, minus the involvement of Holliday, was described briefly in the first movie, and more fully in the pseudo-documentary Curse of the Blair Witch, which accompanied the movie DVD.
The main antagonist of the series is not actually the Blair Witch, but a demon called Hecaitomix. It's explained through the game and the series that this demon controlled and possessed others, like Elly Kedward, and (through Kyle Brody) influenced Rustin Parr.
The game has reference to Nocturn. Some characters from Nocturne appear at the start of the game: Master Khen Rigzin, Coronel Hapscomb, General Biggs, an unnamed secretary, Svetlana Lupescu, and The Stranger. The Stranger reappears later in the game, on the fourth day, as the player's partner. Some enemies from Nocturne (the bat creatures, a werewolf) also appear in the beginning of the game, in the training session.
While he heals, he has a number of hallucinations and a near-death experience, in which he learns, but does not fully comprehend, that Robin is in danger. When he awakes, it is discovered that he is suffering from amnesia, and cannot remember who he is. The only clue to his past is the uniform he wears. Since he cannot remember his name, Robin's grandmother, a devout Christian, temporarily names him Lazarus.
Robin's grandmother, with the soldier now in her debt, informs him that Robin has disappeared into the woods and begs him to find her. She is convinced that "the woods have her". The soldier regards this as paranoia, and thinks that Robin has simply gone to play in the woods and is late in returning. Bess is insistent, however, and the soldier reluctantly agrees to help in the search for Robin.
As the game progresses, Lazarus recalls elements of his past, by means of flashback game sequences, which slowly explain how the current events come to be.
Elly Kedward was accused of witchcraft after it was found she had been drawing blood from the local children and performing pagan rituals. She was tried, convicted and sentenced to be banished from the town. The locals tied her to a wheelbarrow, dragged her into the nearby woods and left her to freeze to death. Kedward disappeared from the wheelbarrow to which she was tied, and was never seen again.
A few days later, children from the township began to disappear, and the population began to flee out of fear - with only the local magistrate, Jonah, and the township's chaplain, Father Hale Goodfellow, remaining behind. Father Goodfellow is convinced that an evil supernatural force is at work - Jonah, a skeptic, refuses to believe this.
There are also two people who are locked in a jail in the town: Hirrum Heathtow is a drunk, and Elizabeth Styler is a witch who was arrested when she was found in Elly's house, reciting strange phrases.
The player must guide Prye through his investigation, to discover what happened to the Blair Witch.