After a suspicious airplane lands in JFK airport, Dr. Ephraim Goodweather is summoned to conduct an investigation with his team into the incident, only to discover that the passengers are actually corpses that carry a terrible virus.
Eph tries to stop the only four people who were found alive aboard the plane from being released, but his boss takes him off the case. Eerie goings-on start taking place as the survivors develop odd symptoms. While in jail, Setrakian is visited by Eichhorst.
In quarantine, Captain Redfern's condition worsens. Eichhorst makes Jim Kent, a CDC employee, a tempting offer to ensure his loyalty. Nora approaches Setrakian, who has been released from jail recently, seeking his help.
Eph and his colleagues are bemused as they perform an autopsy on Redfern's body. Jim comes clean to Eph about his misconduct. Setrakian slays two infected humans and asks Eph and Nora to join him in his mission to annihilate all those infected.
Eph decides to help Setrakian, hoping to find proof to support his claim in order to show it to his boss, but he finds himself accused of Redfern's murder. Exterminator Fet makes a terrible discovery. In a flashback, Setrakian meets Eichhorst for the first time.
While trying to warn his estranged wife to leave the city with their son, Eph is apprehended by the FBI. Nora seeks shelter in Setrakian's pawnshop with her mother. With an eclipse approaching, Setrakian fears that the strigoi will attack humans in the daytime as well.
In an attempt to redeem himself, Jim joins forces with Eph and Nora, agreeing that they use him as a decoy to locate the Master. Elsewhere, the transformed Joan Luss attacks her husband who has just returned from a trip, while Neeva strives to keep the Luss children safe.
Eph, Nora, Setrakian, and Jim decide to stock up on ultraviolet lamps upon finding out that the strigoi are vulnerable to ultraviolet light. As they go to a convenience store, they meet Fet, who drew the same conclusion. The group gets trapped inside the store as the strigoi make a sudden attack.
After arriving at his house in Queens, Eph saves his son before he gets infected but finds his wife missing. Dutch confesses to helping Eldritch Palmer. Following Felix's transformation, Gus is left with a tough decision to make.
As Eph tries to locate Kelly, he goes to her friend Diane's house, only to find its occupants infected, inferring that the turned Kelly attacked them. Fet tries to help Dutch right her wrong, but things don't go as planned.
Eph sets out to find the Master's lair, along with Setrakian, Fet, and Nora, who refuses to stay behind. Zach comes face-to-face with a strigoi after he tries to procure cigarettes for Nora's mother, only to be saved by Gus.
After the group returns to the pawnshop, Dutch arrives, proposing a plan to televise Eph's warning about the viral outbreak that turns humans into strigoi; however, Eichhorst and a horde of strigoi attack the shop. The Master visits the dying Palmer.
With Fet's help, the group locates the Master's empty coffin. Palmer and Eichhorst force CDC Director Everett Barnes to join them. As Gus learns from Vaun that the Master must be slain by a human, Gus agrees to take him on.