SummaryArtisanal and small-scale gold mining (ASGM) is the leading source of mercury (Hg), a global neurotoxin. Past research has focused on the health impacts on miners and nearby residents; here, we estimate the risk for global general populations by employing a comprehensive atmosphere-land-ocean-ecosystem and exposure-risk-valuation model framework. Our results suggest that ASGM sources contribute 12%, 10%, and 0.63% to the atmospheric Hg deposition, plankton methylmercury concentrations, and soil total Hg concentrations at present day, respectively, and cause 5.8×105 points of intelligence quotient decrements and 1,430 deaths for global general populations per year. The monetized global health impact of ASGM ($154 billion) is 1.5 times its local impact and accounts for half of the total revenue of ASGM ($319 billion). A major spatial decoupling between the health impact and economic gains is also revealed, suggesting that intervention measures such as awareness-raising, capacity-building, and technology transfer funded by the Global North are cost-effective.