The Tonle Sap Lake (TSL), one of the world’s most productive lake–wetland ecosystems is sustained by an annual flood pulse that reverses Lower Mekong River flow into the lake during the monsoon and returns freshwater downstream during the dry season. Recent declines in the reverse flow have previously been attributed to climate change and upstream damming. However, here we show that between 1998 and 2018, riverbed lowering of the Mekong mainstem, driven by sand mining and upstream sediment trapping, has reduced the reverse flow by between 40 and 50% (high- to low-flow year range; 47% for medium flows). Projections to 2038, with additional riverbed lowering driven by ongoing sand mining, predict reverse flow declines of 69% (64–73%) compared with 1998. We show how these changes affect the lake’s flow regulation services across the Lower Mekong system. Specifically, the reduced TSL reverse flow increases flows to the Mekong Delta by ~26 km3 (31–23 km3) during the monsoon, heightening flood risk, while decreasing dry-season flows by ~59% (50–61%), contributing to intensified saltwater intrusion and diminished agricultural yields across the Mekong’s Delta. Our results underscore how excessive sand extraction is an existential threat to the TSL–Mekong system’s sustainability
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