A sudden, inexplicable death at a wedding celebration triggers a series of supernatural events that threaten the lineage of the usurper Manfred. Manfred, the lord of Otranto, seeks to secure his family's future through marriage and inheritance, but he finds himself thwarted by ancient prophecies and spectral manifestations. As he attempts to manipulate those around him, he faces opposition from both the rightful heirs and the mysterious forces haunting his castle. The narrative utilizes a dramatic, heightened tone to explore themes of tyranny, guilt, and the weight of ancestral sins within a claustrophobic, labyrinthine setting.

Discussion often centers on the work's status as the foundational text of the Gothic genre, establishing tropes that would influence literature for centuries. Readers frequently highlight the rapid, almost frantic pacing that prioritizes immediate sensation over slow-burn character development. Critics often note the intentional artifice of the prose, which reflects the author's desire to bridge the gap between medieval romance and contemporary realism. The atmospheric density of the castle setting is frequently cited as a primary element that sustains the reader's interest despite the stylized and sometimes archaic dialogue.