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Global mangrove loss has been attributed primarily to human activity. Anthropogenic loss hotspots across Southeast Asia and around the world have characterized the ecosystem as highly threatened, though natural processes such as erosion can also play a significant role in forest vulnerability. However, the extent of human and natural threats has not been fully quantified at the global scale. Here, using a Random Forest-based analysis of over one million Landsat images, we present the first 30 m resolution global maps of the drivers of mangrove loss from 2000 to 2016, capturing both human-driven and natural stressors. We estimate that 62% of global losses between 2000 and 2016 resulted from land-use change, primarily through conversion to aquaculture and agriculture. Up to 80% of these human-driven losses occurred within six Southeast Asian nations, reflecting the regional emphasis on enhancing aquaculture for export to support economic development. Both anthropogenic and natural losses declined between 2000 and 2016, though slower declines in natural loss caused an increase in their relative contribution to total global loss area. We attribute the decline in anthropogenic losses to the regionally dependent combination of increased emphasis on conservation efforts and a lack of remaining mangroves viable for conversion. While efforts to restore and protect mangroves appear to be effective over decadal timescales, the emergence of natural drivers of loss presents an immediate challenge for coastal adaptation. We anticipate that our results will inform decision-making within conservation and restoration initiatives by providing a locally relevant understanding of the causes of mangrove loss.