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Abstract A disproportionate share of the global economic and human losses caused by environmental shocks is borne by people in the developing nations. The mountain region of Hindu-Kush Himalaya (HKH) in South Asia is threatened by numerous flooding events annually. An efficient disaster risk reduction often needs to rest upon location-based synoptic view of vulnerability. Resolving this deficit improves the ability to take risk reduction measures in a cost-effective way, and in doing so, strengthens the resilience of societies to flooding disasters. The central aim of this research is to identify the vulnerable locations across HKH boundary from the perspective of reported history of economic and human impacts due to occurrence of flooding disasters. A detailed analysis indicates a very high spatial heterogeneity in flooding disaster occurrence in the past 6 decades. The most recent decade reported highest number of disasters and greater spatial coverage as compared to the earlier decades. The data indicates that, in general, economic impacts of flooding disasters were notably higher in Pakistan, Afghanistan and Nepal. On the other hand, vulnerability scenarios with respect to human impacts were diverse for different countries. In terms of morbidity and mortality, Bangladesh, Pakistan, Bhutan and India were detected to be most susceptible to human impacts. Although Bhutan had seen lesser number of flooding disasters, higher population living within disaster prone region make them vulnerable. In summary, complex interactions between natural and socio-economic conditions play a dominant role to define and characterize the type and magnitude of vulnerability of HKH countries to disaster occurrence and their economic and human impacts.