The narrative opens within the gloomy halls of Otranto, where Prince Manfred is fiercely determined to secure his dynasty through the marriage of his sickly son, Conrad. On the morning of the wedding, a grotesque and impossible catastrophe destroys the young groom: a gigantic, plumed helmet falls from the sky, crushing him instantly. Driven by frantic ambition and a dread of ancient prophecies foretelling the loss of his domain, Manfred abruptly turns his sights on Isabella, his late son's betrothed, resolving to divorce his virtuous wife Hippolita and marry the terrified young woman himself. Isabella flees into the subterranean vaults of the castle, aided by a mysterious young peasant named Theodore who shares an uncanny resemblance to the castle's former rightful ruler, Alfonso.
As the pursuit intensifies, the castle is shaken by increasingly bizarre preternatural occurrences, including sighing portraits and moving architectural elements. Frederic, the rightful Marquis of Vicenza and Isabella's long-lost father, arrives with an imposing armed retinue to claim both his daughter and his ancestral lands. Complications multiply as romantic tensions intertwine with political claims. Theodore, imprisoned by the tyrant Manfred, repeatedly risks his life to shield the innocent, and his true identity becomes the central puzzle of the unfolding tragedy. The narrative shifts between secret pursuits in subterranean labyrinths, theological disputes with the local friar Jerome, and the heavy burden of ancestral curses.
The emotional weight of the novel centers on the quiet suffering of Hippolita and her gentle daughter Matilda, both of whom exhibit unwavering loyalty despite Manfred's escalating cruelty. Misunderstandings and mistaken identities in the dark create a network of peril. Theodore proves his valor in single combat against Frederic’s champion, only to discover a deeper familial bond that ties him to the lineage of Alfonso. The climax approaches as secrets of birth and rightful succession are dragged into the light, threatening to dismantle the usurper's power once and for all.
In the tragic denouement, the convergence of divine justice and human error culminates in a devastating accident within the sacred walls of St. Nicholas's church. Manfred, blinded by rage and darkness, strikes a fatal blow meant for another, only to destroy his own daughter Matilda. The crumbling of the castle's physical structure mirrors the absolute collapse of the usurping house, clearing the way for Theodore to claim his rightful heritage alongside a chastened and sorrowful court.