This article analyses long-term population dynamics—growth, decline, sex- and age-composition—in Chaghadaid-era Central Asia in the context of the ‘Late-medieval Crisis’. It is based on a unique dataset of 630 epitaphs from two East Syriac (‘Nestorian') graveyards in the Semirech'ye region (Northwest Tian Shan, North Kyrgyzstan), boosted by archaeological and osteological evidence from the same graveyards. This epigraphic corpus is truly unique in the sense that this is the only surviving data that allow the undertaking of such a quantitative reconstruction of pre-modern Central Asian demography. A close analysis of the corpus, based on the ‘excess mortality’ method, reveals rapid demographic growth between circa 1270 and 1330, despite frequent short-term mortality crises, caused, most likely, by a combination of environmental and political factors. The population growth came to a sudden halt because of a major plague outbreak in 1338–1339, killing about three-quarters of the local population, and initiating what was known as the Black Death of 1347–1353 in West Eurasia and North Africa. The analysis of sex and age ratios indicates that the local population regime was heavily male-dominated. The plague of 1338–1339 targeted primarily younger women, most likely due to pregnancy-related hazards; conversely, in other crisis years, adult males were more susceptible. The findings of the article are wrapped into the wider context of the ‘Late-medieval Crisis’.