Background: In 2010, Médecins Sans Frontières discovered a lead poisoning outbreak linked to artisanal gold processing in northwestern Nigeria. The outbreak has killed approximately 400 young children and affected thousands more. Objectives: Our aim was to undertake an interdisciplinary geological- and health-science assessment to clarify lead sources and exposure pathways, identify additional toxicants of concern and populations at risk, and examine potential for similar lead poisoning globally. Methods: We applied diverse analytical methods to ore samples, soil and sweep samples from villages and family compounds, and plant foodstuff samples. Results: Natural weathering of lead-rich gold ores before mining formed abundant, highly gastric-bioaccessible lead carbonates. The same fingerprint of lead minerals found in all sample types confirms that ore processing caused extreme contamination, with up to 185,000 ppm lead in soils/sweep samples and up to 145 ppm lead in plant foodstuffs. Incidental ingestion of soils via hand-to-mouth transmission and of dusts cleared from the respiratory tract is the dominant exposure pathway. Consumption of water and foodstuffs contaminated by the processing is likely lesser, but these are still significant exposure pathways. Although young children suffered the most immediate and severe consequences, results indicate that older children, adult workers, pregnant women, and breastfed infants are also at risk for lead poisoning. Mercury, arsenic, manganese, antimony, and crystalline silica exposures pose additional health threats. Conclusions: Results inform ongoing efforts in Nigeria to assess lead contamination and poisoning, treat victims, mitigate exposures, and remediate contamination. Ore deposit geology, pre-mining weathering, and burgeoning artisanal mining may combine to cause similar lead poisoning disasters elsewhere globally.