When a plane lands in New York City with everyone on board dead, Dr. Goodweather, head of the CDC's Canary Project, and his team are called upon to investigate. A pawnbroker races to the airport convinced this is the beginning of something sinister.
The four survivors begin manifesting strange symptoms, but Eph and Nora’s attempt to quarantine them is thwarted as the disinformation campaign begins. Meanwhile, in jail, Setrakian receives a surprise visit from 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 to Fet that something inexplicable is happening deep below the city.
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.
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, and 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, while Setrakian realizes that the coming eclipse is a tipping point for virus infection.
Setrakian, Eph, and Nora formulate a plan to track down the Master using Jim as bait. Eichhorst and Setrakian's pasts are revealed. Neeva struggles to protect the children while encountering a mysterious stranger whose help she may not want.
Dutch returns with a plan to broadcast Eph’s warning about the vampiric plague. However, they face a new threat when Eichhorst launches his own attack against the pawn shop. Palmer receives a special visitor, and Gus gears up for the oncoming fight.
Kenny, who knows he's stronger, offers up his sister Miriam to compete in a bench press competition. Spenny takes the challenge, not fully realizing that if he loses to Kenny's sister, it will be the most humiliating defeat he's ever suffered.
After Teressa and Christian steal Declan's cartel shipment, he must forge an alliance with Alex LaChance, head of the Devil's Kings biker gang to get it back before his five million dollars payment is due.