Chronic exposure from drinking well-water with naturally high concentrations of fluoride (F^–) has serious health consequences in several regions across the world including South Asia, where the rural population is particularly dependent on untreated groundwater pumped from private wells. An extensive campaign to test 28,648 wells was conducted across the Punjab plains of Pakistan and India by relying primarily on field kits to document the scale of the problem and shed light on the underlying mechanisms. Groundwater samples were collected from a subset of 712 wells for laboratory analysis of F^– and other constituents. A handful of sites showing contrasting levels of F^– in groundwater were also drilled to determine if the composition of aquifer sediment differed between these sites. The laboratory data show that the field kits correctly classified 91% of the samples relative to the World Health Organization guideline for drinking water of 1.5 mg/L F^–. The kit data indicate that 9% of wells across a region extending from the Indus to the Sutlej rivers were elevated in F^– relative to this guideline. Field data indicate an association between the proportion of well-water samples with F^– > 1.5 mg/L and electric conductivity (EC) > 1.5 mS/cm across six floodplains and six intervening doabs. Low Ca²⁺ concentrations and elevated bicarbonate (HCO₃^– > 500 mg/L) and sodium (Na⁺ > 200 mg/L) in high F^– groundwater suggest regulation by fluorite. This could be through either the lack of precipitation or the dissolution of fluorite regulated by the loss of Ca²⁺ from groundwater due to precipitation of calcite and/or ion exchange with clay minerals. Widespread salinization of Punjab aquifers attributed to irrigation may have contributed to higher F^– levels in groundwater of the region. Historical conductivity data suggest salinization has yet to be reversed in spite of changes in water resources management.