We studied Tibet's Qamdo City, which currently hosts the most serious prevalence of Kashin-Beck osteoarthropathy (KB) in China. This study utilizes the geographical detector (GeoDetector) algorithm to measure the individual and interactive influences of risk factors on KB and to quantify the highest potential risk subzones of each principal factor. With a comprehensive consideration of 13 possible related factors, namely, the tectonic division, stratum, moisture index, gross domestic product, mean annual precipitation, soil type, groundwater type, elevation, mean annual temperature, vegetation type, geomorphic type, slope degree and slope aspect, our results indicate that the main exposure factors for KB in Qamdo City are geological factors (tectonic division and stratum), wetting factors (moisture index and mean annual precipitation), and an economic factor (gross domestic product). In contrast, other factors have little effect on the prevalence of KB in Qamdo City. All 13 factors either nonlinearly or bivariately enhance each other, and the interactions between these factors can increase the prevalence of KB. Consequently, it can be inferred that KB in Qamdo City is caused primarily by a set of multiple and interrelated disease risk factors.