The purpose of this study is to examine the descriptions of the transmission of plague along the Silk Road in Orhan Pamuk’s 2022 novel Nights of Plague. Pamuk won the Nobel Prize in Literature in 2006, the first prize for Turkish literature. Pamuk’s vast knowledge of epidemiological history, which has long fascinated him, comes to life in this novel as he describes the characters’ battles against the plague in the East and West and how the plague was brought to the islands and spread along the Maritime Silk Road. One of the most important trade routes in human history, the Silk Road was not only a link between East and West trade and cultures but also a route for the transmission of bubonic plague during the medieval period onwards. It was this epidemic that contributed to the decline of the Silk Road. In the novel, a plague originating in China strikes the Ottoman coastal cities of Smyrna and Mingheria on its way to Europe via India. The epidemic is contained in Smyrna but the death toll spirals out of control when the plague reaches the island of Mingheria by sea. The spatial setting of the novel is an island, which means that it communicates with the outside world by sea. The only way the plague could have spread to an isolated island was by ship. Rats from different ports and ships would have traveled to other parts of the world or even countries to spread the plague. In Nights of Plague, the fact that the plague reached Mingheria via the maritime Silk Road is also proven by the route of the ships and various narratives. The novel confirms what many scholars have argued, that the Silk Road brought various goods from the East to the Roman Empire, along with deadly diseases, and that the sea routes were an important way for the plague to travel and spread.