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Uranium and fluoride enrichment in groundwater along alluvial plains pose a severe threat to living beings like cancer, fluorosis and crop yield as witnessed around semi-arid southwest Punjab, India. In-situ groundwater was examined for major ions, stable isotopes and trace metals to understand the hydrogeochemical processes, contaminant origin and health risks around SW Punjab, India. Groundwater from a freshly drilled bore well is found to be hard, alkaline, and saline with total dissolved solids and salinity up to 1300 and 1500 mg L−1, respectively. Fluoride (up to 4 mg L−1) and uranium (up to 90.07 μg L−1) contents exceed permissible limits in most samples and originated from fertilizer inputs and aquifer leaching. Uranium contents decline with depth, while fluoride remains invariable. Decreased U contents are inferred to be caused by U(VI) reduction to U(IV) as evidenced by an increase in Fe2+ vs. Fe3+, S2− vs. S6+ and N3− vs. N5+ with depth. NaHCO 3 , NaCl + NaHCO 3 and NaCl are the dominant water types for shallow (<38 m), intermediate (49–83 m) and deeper groundwater (105–128 m) with Na+ and HCO 3 − as the dominant cations and anions, respectively. Silicate weathering majorly controlled the groundwater geochemistry together with a partial contribution from cation exchange processes. Unsuitability for drinking and irrigation use is envisaged for all depths, while deeper groundwater is safe in regard to radiological risk. δ18O and δD variations are suggestive of evaporation dominance in shallow groundwater, while intermediate groundwater witness canal and groundwater mixing and deeper groundwater are recharged through higher altitude. [Display omitted] • Alkaline and saline groundwater with high dissolved solids and unsafe for direct use. • Na+, HCO 3 − and Cl− constitute the dominant ions with NaHCO 3 and NaCl water types. • Silicate weathering and cation exchange dominantly control hydrogeochemistry. • δ18O/δD signify evaporation, canal-groundwater mixing and high altitude recharge. • Fertilizer inputs and aquifer soil leaching combinedly contribute excess U and F. [ABSTRACT FROM AUTHOR]