Innumerable studies have emphasized elevated fluoride (Fˉ) and uranium (U) levels in shallow aquifers in the semi-arid region of Punjab, India, endangering the groundwater-dependent population’s health. This study examines the factors and mechanisms contributing to Fˉ and U co-occurrence in the region’s aquifers to enhance the understanding of the contaminants’ behaviour. Fˉ and U concentrations were higher in shallow aquifers (<60 m) compared to deeper (>60 m), and both the contaminants surpassed their respective permissible limits under excess EC, TDS, salinity, Clˉ, NO3ˉ, SO42ˉ, Na+, and K+ levels. Elevated EC and TDS and their strong correlation with U and Fˉ facilitated mobilization and co-contamination via increased ionic strength and competitive behaviour through ion exchange mechanism. Scanty precipitation, enhanced evapotranspiration, and aridity were also significantly correlated to Fˉ and U, highlighting the key aspect of meteorological conditions on groundwater co-contamination, particularly in the Malwa region. The mixed chemical composition of the groundwater emanated from rock-water interaction and evaporation, which further increased Fˉ and U and facilitated their co-occurrence. U existed predominantly as UO2(CO3)22ˉ and UO2(CO3)34ˉ (95%), which corroborated with a strong positive correlation with HCO3, whereas fluoride existed mainly as free Fˉ (90%). The findings of this work will help the scientific community to address similar issues in other arid and semi-arid regions globally and investigate the potential synergistic effect and health risks associated with the co-occurrence of Fˉ and U in the groundwater.