Did the Black Death, the famous, devastating plague pandemic that struck the Mediterranean and Western Europe in the mid-14th century and seeded new strains of the pathogen, Yersinia pestis, in new locales, also reach Sub-Saharan Africa? That it reached the Islamic North African littoral has never been in question: there is ample testimony from Arabic documentary sources for its devastating effects from Egypt to the Maghreb. But did it stop there? Archaeologists now have reason to believe that there was widespread abandonment of urban communities in West Africa in the 14th or 15th centuries. Focusing on the other side of the continent, the present essay argues that previously unutilized evidence—a “living archive” of genetic data combined with a new reading of linguistic and documentary evidence from the 14th through 20th centuries—suggests that plague did have a significant impact on pre-modern East Africa. The strains of Y. pestis currently found in East and Central Africa derive from one of the lineages involved in late medieval outbreaks in Central Eurasia. This post-Black Death strain, it is argued here, entered the continent most likely in the late 15th or early 16th century. This coincides with hitherto unexplained population migrations and other cultural signs of reactions to a deadly emerging disease. Although no aDNA (historical genetic material) for Y. pestis has yet been recovered from late medieval or early modern Africa, the present essay suggests that evidence for Y. pestis’s evolution and transcontinental movements, even those outside of Africa, can help archaeologists and historians draw Africa more centrally into the narratives of global history.