A young boy, Thomas Grey, is walking through the forest when he sees a girl picking berries. She sees Thomas and asks if he wants to play, and then dares him to chase her. She runs off and Thomas goes after her. However, the girl disappears into thin air and a horseman gallops toward Thomas, who runs in terror. He finally stumbles out through the trees onto the highway, and the horseman disappears.
Abbie and Ichabod bring some supplies to Corbin's cabin so that Ichabod can settle in there rather than stay at the hotel. She notes that it's perfect for Ichabod and wonders if Corbin knew that all along. As they unpack, Ichabod checks himself in a hand mirror and wonders if he looks out of place, and Abbie assures him that he looks fine. They receive a routine call about a boy turning up and Ichabod insists on going with Abbie, warning that they may not have any routine calls anymore.
When they arrive at the fountain where Thomas was found, Abbie and Ichabod confirm that a mail carrier saw the boy emerge from the woods earlier. Luke is there with his partner Devon and he asks Abbie is she's sick of babysitting Ichabod. She ignores him, while Ichabod checks Thomas' hands and discovers that they have protruding black veins. Thomas is wearing old-fashioned clothing and says something in Middle English, and Ichabod realizes what he's saying. He tries to talk to the boy in the same tongue but the EMTs take Thomas away before Ichabod can get anything out of him.
The next day, Abbie is checking child abduction records while Ichabod informs her and Irving that Thomas said "evil girl." They've checked all of the towns in the area, even Amish communities, but no one has reported a boy matching Thomas' description. Irving has called in the CDD and they're sending a man, Parsons, to determine if the disease that Thomas has is contagious. As the captain goes to his office, Luke approaches him and suggests that Ichabod being brought on as a consultant after his arrest for murder is making some people in town nervous. Irving figures that Luke is jealous and asks if his history with Abbie is going to cause problems, and Luke assures him that it won't.
Ichabod and Abbie go to the hospital to talk to Thomas as the staff quarantine the boy and evacuate the patients in case of a contagious disease. Parsons has Ichabod speak to Thomas via a closed camera system and tells him to find out anything the boy knows about the infection. Ichabod introduces himself and confirms Thomas' name, and Thomas apologizes, saying that he wasn't supposed to run off. The boy says that he's from Roanoke, Virginia, and Parsons and Abbie start making calls to Roanoke. However, Ichabod suggests that Thomas came from the lost colony of Roanoke, where an entire population of settlers disappeared without a trace in 1587.
When they return to the archive, Ichabod tells Abbie that when Gov. John White of Roanoke returned to England for supplies, he was unable to return until three years later. He left his daughter Eleanor behind and she had Virginia, the first British child born on American soil. When the governor returned, every colonist had disappeared without at race. Ichabod suspects that Thomas may have come from the original colony, or be a descendent of someone who did. Irving calls to tell Abbie that Thomas is getting worse, and that the EMT that brought Thomas in is similarly infected. Ichabod and Abbie tell the captain that they'll go the forest where Thomas was spotted and try to determine where he came from.
At the hospital, the EMT is in extreme pain from the disease. He looks up past the doctors and sees a horseman bearing down on him.
As Abbie drives to the forest, they see residents panicking and packing up to leave.
At the station, Irving tells Luke and Devon to meet him at the hospital in thirty minutes Devon asks if Luke if he went to the captain about their concerns about Ichabod, and Luke admits that Irving shut him down. Devon figures that if they can solve the current case then they can get a promotion and tells Luke to ignore his concerns about Ichabod.
Ichabod follows Thomas' trial back through the forest and they find another set of girl's footprints. They realize that they belong to the evil girl Thomas spoke of but discover that the footprints disappear as if the girl had vanished into thin air.
At the hospital, Luke and Devon inform Irving that two more people have come down with the disease. Irving updates Parsons on their search for where Thomas came from, and Parson says that Thomas' blood panels show no sign that he ever had a vaccination. The CDC has never seen anything like the disease that Thomas has and can't treat it until they identify it.
Ichabod follows Thomas' trail to a small river and points out a small island across the water. He tests the water and finds it too deep to cross, even though only Thomas' feet were wet. After a moment, Ichabod steps out onto the water... and stands on top of it. He tells Abbie that there are markings on the nearby trees indicating a hidden crossing just beneath the water and gestures for her to join him. Once they go across they find an entire 16th century village on the island... complete with settlers. As Ichabod and Abbie enter the settlement, they realize that all of the residents have the black veins on their skin. Ichabod questions them in Middle English and they explains that they're in Roanoke.
As they go to the meeting house, Abbie notes that the settlers aren't suffering from the disease. Ichabod speaks with the prefect, who explains that one of the Horsemen, Pestilence, cursed the original Roanoke colony. Virginia was the first to die, and her spirit led the settlers to their new location to protect them. As long as they remain in the settlement, they keep the disease with them and it can't infect the outside world. The Horseman lured Thomas into leaving and going into the outside world, where he will unleash the plague. When it takes hold, the Horseman will be able to fully manifest. The prefect asks them to bring Thomas back to save the dying victims in the outside world.
At the hospital, one of the CDC medics checks on Thomas... unaware that her suit has a rip in it.
As Ichabod and Abbie prepare to head back, Ichabod figures that Virginia is protecting the settlers, just as Katrina protects him. he figures that the settlement is the key to stopping the Horseman, and hopes that by bringing Thomas there they can stop Pestilence before he manifests. As they go, one girl standing by the town spring offers Abbie a flower. She gently refuses and then sees Pestilence in the distance, lurking on the edges of the settlement. She tells Ichabod that they have to go, and he promises the prefect that they will bring Thomas back.
As they drive back to Sleepy Hollow, Abbie warns Ichabod that the CDC won't release Thomas for fear of contagion. They go inside and Ichabod realizes that he has become infected as well from contact with Thomas at the fountain. Parsons has a hazmat team sedate Ichabod and take him away rather than let him go and risk contagion.
Ichabod finds himself in purgatory where his wife Katrina is trapped. She finds him and realizes that if he is there, then it means that he is dead or close because Moloch has blocked her from summoning him.
Luke calls Oxford and learns that Ichabod's credentials turn out to be authentic. Unaware that Irving has set up Ichabod's fake credentials, Luke talks to the captain, who tells him to work with Parsons to prepare a plan for public containment. Irving then watches Ichabod on the monitors.
Ichabod admits that he's sick and she fears that he will soon die. Other persons move around them and Katrina explains that they are trapped in purgatory like herself, and Moloch is the one who sends them on to wherever he chooses.
Abbie tells Irving what they discovered and insists that they have to get Ichabod and Thomas out of the hospital and back to the settlement. Irving refuses, warning that it would cause a panic and risk contagion, and tells her to check in with Luke and get her assignment. Once the captain leaves, Abbie ducks away and finds herself in the hospital chapel.
Ichabod realizes that there's something that Katrina isn't telling him.
Abbie sits down in the chapel and asks God if he's putting her through some kind of trial.. She wants a sign that shows that Thomas will be okay if she takes him back to the settlement. Abbie gets no response and gets up to leave. A woman comes in, touching the font water, and Abbie remembers the spring at the settlement... and realizes that it's the key.
Katrina finally starts to tell her husband why she is trapped in Purgatory, but he wakes up in the real world and his spirit leaves purgatory.
In the control room, Abbie tells Irving that the water in the Roanoke spring holds the cure to the disease. Irving is surprised that she believes it can work since she's going on faith, and Abbie says that she doesn't have any other choice. Irving agrees to create fake orders transferring Ichabod and Thomas, and Abbie can drive them away. Once he puts the orders through, Abbie steals the ambulance once the two patients are inside and drives off.
The next morning, Abbie drives to the forest and drags Ichabod and Thomas through the woods. Ichabod tells Abbie that he saw his wife, trapped in purgatory. Thomas collapses and Ichabod realizes that the boy is close to death. Realizing that he's too weak to continue, Ichabod tells Abbie to go on without him. She points out that she can't find Roanoke without his help and gives him a shot of adrenaline. They get to the settlement as the Horseman rides down on them, stronger by the second as Thomas draws closer to death. Ichabod grabs the boy and jumps into the spring, fully immersing himself and Thomas. Pestilence rides directly for Abbie, prepares to kill her... and vanishes.
The settlement explodes in a burst of brilliant white light and Abbie and Ichabod find themselves standing amidst the ancient ruins of the settlement. The ghosts of the settlers walk away with Thomas and Ichabod realizes that they were dead the entire time. He figures that Pestilence lured Thomas away, making himself flesh and blood so that he could spread the plague. Ichabod thanks Abbie, telling her that her faith as a Witness was what led her to the solution. Irving calls and tells Abbie that all of the patients are recovering and the threat is over. As they go back, Abbie wonders if Ichabod considered staying with the settlement, among people of his own kind. When she tells him that he belongs in Sleepy Hollow, no matter how strange he may feel there, Ichabod nods and says that they should be heading home.
That night at the river, the Headless Horseman emerges and rides off into the night.