Season one begins the story of Dr. Ephraim Goodweather, the head of the CDC Canary Team in New York City. He and his team are called upon to investigate a viral outbreak with hallmarks of an ancient and evil strain of vampirism. As the strain spreads, Eph and his team wage war for the fate of humanity itself.
When a plane lands in New York City with everyone on board dead, Dr. Ephraim 'Eph' Goodweather, head of the CDC’s Canary Project, and his team are called upon to investigate. What looks at first like a mysterious viral outbreak might be the beginning of something infinitely more sinister.
The four survivors begin manifesting strange symptoms, but Eph and Nora's attempt to quarantine them is thwarted as the disinformation campaign begins. Setrakian receives a surprise visit from an old – a very old – acquaintance.
Eph and Nora fight to save Captain Redfern's life before coming face-to-face with the horrifying effects of the virus. A spike in rat attacks signals Fet that something inexplicable is happening deep below the city. Released from jail, Setrakian begins his own merciless plan to stop the spread of the disease.
A secret autopsy demonstrates the bizarre progression of the mystery virus, prompting Jim to make a startling confession. Eph and Nora race to find the father of the youngest victim of the plane tragedy, but someone unexpected beats them to it. Ansel, in the grip of disease, takes desperate measures to protect his family.
With Nora gone, Eph reluctantly joins Setrakian's quest in hopes of gathering enough evidence to warrant a citywide quarantine. Fet encounters the unexpected inside the subway tunnels. A medical emergency threatens Palmer's master plan.
After warning Kelly to leave the city with Zack ahead of the spreading plague, Eph is arrested by the FBI. Eichhorst has one final job for Gus. Setrakian realizes that the coming eclipse is the tipping point for virus infection and the beginning of the end.
Setrakian, Eph and Nora formulate a plan to track down the Master using Jim as bait. Eichhorst and Setrakian’s pasts are revealed. At the Luss home, Neeva struggles to protect the children while encountering a mysterious stranger whose help she may not want.
After discovering the potency of ultraviolet light against the strigoi, Setrakian gains a new and unlikely disciple. A quick trip to a Brooklyn convenience store turns into a deadly all-night siege.
Eph races to safeguard his family, only to learn that Kelly is missing. Dutch reveals her role in Palmer’s plan. Gus is forced to make a difficult decision about Felix.
Eph investigates Kelly’s disappearance and struggles with what he finds. Dutch pursues a plan to retaliate against Palmer. Fitzwilliam makes a surprising choice.
Setrakian leads Eph, Fet and Nora in the hunt for the Master's lair. Left behind at the pawnshop with Mariela, Zack risks his safety for Mariela's sake.
Dutch returns with a plan to broadcast Eph’s warning about the vampiric plague, but they face a new threat when Eichhorst launches his own attack against the pawn shop. Palmer receives a special visitor. Gus gears up for the on-coming fight but discovers there’s another mysterious factor involved.