We review the ecological and socio-economic impacts of the catastrophic dam failure in Mariana, Brazil. Tailing management practices by Samarco mining company ultimately caused a dam breach that abruptly discharged between 55 and 62 million m3 of tailings into the Doce River watershed. On November 5th, 2015, a tsunami of slurry engulfed the small district of Bento Rodrigues, loading the Doce River and its estuary with toxic tailings along a 663.2 km trajectory, extending impacts to the Atlantic coast. Acute ecological impacts will adversely affect livelihoods of more than 1 million people in 41 riparian municipalities by reducing local access to fisheries resources, clean water, crop production sites, hydroelectric power generation and raw materials. The threats to riverine human communities are particularly critical for the disadvantaged populations from remote areas that rely on subsistence agriculture and fisheries, and are uniquely vulnerable to long-term heavy metal exposure. At the landscape scale, we predict multiple negative impacts, ranging from alterations of the genetic diversity of fish populations to long-term vegetation loss and poor regeneration in contaminated areas. Consequently, compromised soil stability and runoff control will increase the risk of further geomorphologic disturbance, including landslides, bank failure and mass movements. We propose spatially explicit long-term monitoring frameworks and priority mitigation measures to cope with acute and chronic risks. We posit that, from a national perspective, disastrous impacts like that of Doce River may become more frequent, given the recent regulatory changes that undermine both institutional governance structures and enforcement of environmental regulation.