Dr. Ephraim Goodweather and his team investigate a plane that lands in New York City with everyone on board dead; pawnbroker Abraham Setrakian is convinced that something sinister is beginning.

The four survivors begin manifesting strange symptoms, but Eph and Nora's attempt to quarantine them is thwarted; Setrakian receives a surprise visit from an old acquaintance.

Eph and Nora fight to save Capt. Redfern's life; a spike in rat attacks signals Fet that something inexplicable is happening below the city; Setrakian begins his own merciless plan to stop the spread of the disease.

A secret autopsy demonstrates the bizarre progression of the mystery virus; Eph and Nora race to find the father of the youngest victim of the plane tragedy; Ansel takes desperate measures to protect his family.

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.

It's the beginning of the end as Setrakian realizes that the upcoming eclipse is the apex for viral infection; meanwhile, Eph is arrested after warning Kelly to leave with Zack before the plague spreads; Eichhorst has one last job for Gus.