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.

Penance creates an amplifier to spread Mary's hope-inspiring song across the city – but first, Mary must find her elusive voice. As danger mounts against her group, Amalia propositions an unlikely ally and sets out to expand the Orphanage's reach. Swann further entangles Augie and Mundi in his business affairs.

While Mundi seeks justice, Amalia and her most trusted advisors make a list of potential enemies. Harriet, Primrose, and the other Orphans attempt to decipher a message. Later, Amalia exposes an unexpected threat.

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.

After Amalia's origin story is revealed, a long-awaited reunion crystallizes the Orphans' mission.