Loosely based on various works by 19th-century author Edgar Allan Poe (most prominently the eponymous 1840 short story), the series adapts otherwise unrelated stories and characters by Poe into a single nonlinear narrative set from 1953 to 2023. It recounts both the rise to power of Roderick Usher, the powerful CEO of a corrupt pharmaceutical company and his sister Madeline Usher, the firm's genius COO, and the events leading to the deaths of all six of Roderick’s children.