London, 1899. Three years after an inexplicable event suddenly equips them with extraordinary abilities, Amalia True and Penance Adair work to protect their kind from widespread, deepening antipathy. Meanwhile, police inspector Frank Mundi investigates a string of murders at the hands of a reportedly Touched and highly dangerous serial killer named Maladie.

With the city reeling from Maladie's opera debut, Mundi takes a personal stake in tracking her down, while Amalia launches an investigation of her own. Meanwhile, the charitable Lavinia Bidlow seeks to destigmatize the Touched at a society event, Hugo Swann enlists Lavinia’s younger brother Augie to help monetize his illicit enterprise, and a deranged doctor conducts a series of experiments.

As the city buzzes with anticipation over a pending execution, Penance grapples with a moral calling at odds with Amalia's plan. With the two women at a crossroads, the Orphans must decide whom to follow.