The show centers around Dr. Ephraim Goodweather, the head of the CDC's New York-based Canary Project, who is called upon to investigate an airplane landing wherein everyone aboard is dead. What his team discovers is a viral outbreak that has similarities to an ancient strain of vampirism. The virus begins to spread and Goodweather works with his team and a group of the city's residents to wage a war to save humanity. As the series progresses, Goodweather finds new allies as they discover a dark underworld, political corruption and a sinister plot for dominion over life.