<p>This study investigates the co-occurrence of uranium (U), fluoride (F), and nitrate (NO₃⁻) in untreated groundwater used for drinking water in the city of Agadez, Niger, with implications for the wider Sahel region. Comprehensive hydrochemical analysis of all public and a cross-sectional sample of private drinking water wells revealed widespread contamination. Among drinking water wells, 63.6% exceeded the WHO guideline for uranium, 68.2% exceeded the fluoride guideline, and 13.6% exceeded the nitrate guideline. Deterministic health risk assessment using USEPA reference doses showed that 77.3% of drinking water wells pose cumulative non-carcinogenic health risks to adults and 86.4% to children (Hazard Index &gt; 1, summed across U, F, and NO₃⁻). Risk levels were slightly higher for private than for public wells, indicating only a minor disparity in exposure across the population. Solute correlation analysis and saturation index calculations, supported by irrigation-well data, indicate distinct geochemical controls on contaminant occurrence. Uranium mobility in Paleozoic–Mesozoic sandstones of the Teloua Formation is enhanced by carbonate complexation in bicarbonate-rich waters, while fluoride released from mica minerals accumulates under alkaline conditions due to calcite–fluorite coupling and calcium depletion. In contrast, nitrate contamination is anthropogenic, with one private drinking water well exhibiting extreme concentrations (3,433&#xa0;mg/L) linked to inadequate sanitation. These results indicate that a significant portion of Agadez’s 124,000 residents are chronically exposed to elevated levels of uranium, fluoride, or both through untreated groundwater sources. Given the regional continuity of similar geological formations and sanitation challenges, comparable multi-contaminant groundwater quality problems could occur across the Sahel. This study represents the first comprehensive assessment of uranium–fluoride–nitrate co-occurrence in Sahelian groundwater.</p>