Homicide detective John Lowe traces a series of grisly murders back to the stylish Hotel Cortez in Downtown Los Angeles and its infamous residents.

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.