Abstract: Despite numerous studies, there are many knowledge gaps in our understanding of uranium (U) contamination in the alluvial aquifers of Punjab, India. In this study, a large hydrogeochemical dataset was compiled to better understand the major factors controlling the mobility and enrichment of uranium (U) in this groundwater system. The results showed that shallow groundwaters (\textless60 m) are more contaminated with U than from deeper depths (\textgreater60 m). This effect was predominant in the Southwest districts of the Malwa, facing significant risk due to chemical toxicity of U. Groundwaters are mostly oxidizing and alkaline (median pH: 7.25 to 7.33) in nature. Spearman correlation analysis showed that U concentrations are more closely related to total dissolved solids (TDS), salinity, Na, K, HCO3−, NO3− Cl−, and F− in shallow water than deep water, but TDS and salinity remained highly correlated (U-TDS: ρ = 0.5 to 0.6; U-salinity: ρ = 0.5). This correlation suggests that the salt effect due to high competition between ions is the principal cause of U mobilization. This effect is evident when the U level increased with increasing mixed water species (Na-Cl, Mg-Cl, and Na-HCO3). Speciation data showed that the most dominant U species are Ca2UO2(CO3)2− and CaUO2(CO3)3−, which are responsible for the U mobility. Based on the field parameters, TDS along with pH and oxidation-reduction potential (ORP) were better fitted to U concentration above the WHO guideline value (30 μg.L−1), thus this combination could be used as a quick indicator of U contamination. The strong positive correlation of U with F− (ρ = 0.5) in shallow waters indicates that their primary source is geogenic, while anthropogenic factors such as canal irrigation, groundwater table decline, and use of agrochemicals (mainly nitrate fertilizers) as well as climate-related factors i.e., high evaporation under arid/semi-arid climatic conditions, which result in higher redox and TDS/salinity levels, may greatly affect enrichment of U. The geochemical rationale of this study will provide Science-based-policy implications for U health risk assessment in this region and further extrapolate these findings to other arid/semi-arid areas worldwide.