Plague was reportedly first introduced to Europe via Genoese traders from their port city of Kaffa in the Crimea in 1347. During a protracted siege of the city, in 1345–1346 the Mongol Golden Horde army of Jani Beg, whose mainly Tatar troops were suffering from the disease, catapulted infected corpses over the city walls of Kaffa to infect the inhabitants, though it is more likely that infected rats travelled across the siege lines to spread the epidemic to the inhabitants. As the disease took hold, Genoese traders fled across the Black Sea to Constantinople, where the disease first arrived in Europe in summer 1347.

The epidemic there killed the 13-year-old son of the Byzantine emperor, John VI Kantakouzenos, who wrote a description of the disease modelled on Thucydides's account of the 5th century BCE Plague of Athens, but noting the spread of the Black Death by ship between maritime cities. Nicephorus Gregoras also described in writing to Demetrios Kydones the rising death toll, the futility of medicine, and the panic of the citizens. The first outbreak in Constantinople lasted a year, but the disease recurred ten times before 1400.