A glacial lake outburst flood (GLOF) is a typical glacier-related hazard in high mountain regions. In recent decades, glacial lakes in the Himalayas have expanded rapidly due to climate warming and glacial retreat. Some of these lakes are unstable, and may suddenly burst under different triggering factors, thus draining large amounts of water and impacting downstream social and economic development. Glacial lakes in the Poiqu River basin, Central Himalayas, have attracted great attention since GLOFs originating there could have a transboundary impact on both China and Nepal, as occurred during the Cirenmaco GLOF in 1981 and the Gongbatongshaco GLOF in 2016. Based on previous studies of this basin, we selected seven very high-risk moraine-dammed lakes (Gangxico, Galongco, Jialongco, Cirenmaco, Taraco, Beihu, and Cawuqudenco) to simulate GLOF propagation at different drainage percentage scenarios (i.e., 25%, 50%, 75%, and 100%), and to conduct hazard assessment. The results show that, when any glacial lake is drained completely or partly, most of the floods will enter Nepal after raging in China, and will continue to cause damage. In summary, 57.5 km of roads, 754 buildings, 3.3 km2 of farmland, and 25 bridges are at risk of damage due to GLOFs. The potentially inundated area within the Chinese part of the Poiqu River basin exceeds 45 km2. Due to the destructive impacts of GLOFs on downstream areas, appropriate and effective measures should be implemented to adapt to GLOF risk. We finally present a paradigm for conducting hazard assessment and risk management. It uses only freely available data and thus is easy to apply.