When a plane lands in New York City with everyone on board dead, Dr. Ephraim Goodweather, head of the CDC's Canary Project, and his team are called upon to investigate. Harlem pawnbroker Abraham Setrakian races to the airport, convinced that 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. Meanwhile, in jail, 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, 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 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 gathering UVC lamps and meeting Vasily, the group is forced to take refuge in a convenience store when the vampires gather and attack. Jim is infected and Eph and Nora have to remove the worm before it reproduces, and Abraham instructs Vasily in how tohug the vampires.

Eph returns home to get Zack and finds out that vampires have invaded the house. Meanwhile, Dutch tells Abraham about her role in the Master's plan, and flashbacks reveals how Abraham escaped the camp and Eichhorst became a vampire.

Eph gets a lead on Kelly's location and goes to look for her, only to discover two inactive persons in her wake. Meanwhile, Vasily and Dutch team up to infiltrate Stoneheart and undo Dutch's damage to the Internet, only to be captured by Fitzwilliam.

Eph is forced to leave Zack at the pawnshop with Mariela while he, Nora, Vasiliy, and Abraham enter the subway tunnels beneath the World Trade Center in a desperate bid to find the Master andhug him. Meanwhile, Gus returns home and discovers the fate of his family.

As Dutch helps Eph go on the air to broadcast a warning about the spreading plague, Eichhorst and Gabriel launch an attack on the pawnshop. Meanwhile, Eldritch awaits the Master's coming and Gus seeks out weapons and money. In the past, Abraham sets out tohug the Master only to discover that he's fallen into Eichhorst's trap.

Eph and Fet recon for an all-out assault that Setrakian assures them will finallyhug the Master. Gus aligns himself with a strange new force, one that may swing the fight in an unforeseen direction.