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The Mekong River, well known for its aquatic biodiversity, is important to the social, physical, and economic health of millions living in China, Myanmar, Laos, Thailand, Cambodia, and Vietnam. This paper explores the social and environmental impacts of several Mekong basin hydropower dams and groupings of dams and the geographies of their impacts. Specifically, we examined the 3S (Sesan, Sekong Srepok) river system in northeastern Cambodia, the Central Highlands of Vietnam, and southern Laos; the Khone Falls area in southern Laos; the lower Mun River Basin in northeastern Thailand; and the upper Mekong River in Yunnan Province, China, northeastern Myanmar, northern Laos, and northern Thailand. Evidence shows that these dams and groupings of dams are affecting fish migrations, river hydrology, and sediment transfers. Such changes are negatively impacting riparian communities up to 1000 km away. Because many communities depend on the river and its resources for their food and livelihood, changes to the river have impacted, and will continue to negatively impact, food and economic security. While social and environmental impact assessments have been carried out for these projects, greater consideration of the scale and cumulative impacts of dams is necessary.