The second plague pandemic in medieval Europe started with the Black Death epidemic of 1347–1353 and killed millions of people over a time span of four centuries. It is commonly thought that after its initial introduction from Asia, the disease persisted in Europe in rodent reservoirs until it eventually disappeared. Here, we show that climate-driven outbreaks of Yersinia pestis in Asian rodent plague reservoirs are significantly associated with new waves of plague arriving into Europe through its maritime trade network with Asia.