On the Mekong River, north of Stung Treng town in northeastern Cambodia, and below the border with Laos, lies an area of riverine seasonally flooded forest designated as an internationally significant Ramsar wetland site because of its exceptional biodiversity and importance to livelihoods. This article reports on the cumulative and cascading impacts of numerous upstream hydropower dams in China and Laos on this vital ecosystem due to the release of water during the dry season, which prevents the flooded forest from undergoing its critically important drying out period. In particular, we investigate the damage being wrought on these flooded forests and on the various species dependent on them. Different species have been variously affected, but some have been largely destroyed. Others are being increasingly impacted. This habitat loss is negatively affecting fisheries, especially for a number of Pangasiidae catfish and Cyprinid carps, which is having an adverse effect on local livelihoods. New dams upriver, and continued high dry-season water from existing dams, are likely to lead eventually to the increased degradation and possibly the eradication of the flooded forests along the mainstream Mekong River, unless measures are taken to address the problem.