<p>Mountain headwaters are widely regarded as pristine reference systems; however, mounting evidence reveals that even these fragile environments are no longer insulated from the pervasive influence of the Anthropocene. We investigated the seasonal variations in hydrogeochemical signatures and isotopic duality (δ¹⁸O, δD) along a 255-km stretch of the upper Ganga River (Gangotri to Haridwar) during monsoon and post-monsoon seasons, using a spatially resolved, process-focused dataset. Our integrative approach incorporated analysis of geogenic structures, anthropogenic influences, entropy-based water quality indices (EWQI), and multivariate statistical evaluations. The findings demonstrate a marked isotopic and hydrogeochemical duality during the monsoon, which diminishes post-monsoon as water chemistry becomes increasingly homogenized through the mixing and buffering of residual monsoon runoff, stored meltwater, and groundwater contributions. This process results in dilute HCO₃⁻–Ca²⁺–Mg²⁺ waters characterized by a weaker geochemical structure but elevated concentrations of diffuse anthropogenic tracers; namely NO₃⁻, K⁺, and Cl⁻. Post-monsoon, reduced discharge and a greater contribution from groundwater induce stronger geogenic structuring; isotopic signatures cluster sequentially through pH and total suspended solids (TSS) before ion compositions, and hydrochemistry transitions toward HCO₃⁻–SO₄²⁻–Ca²⁺–Mg²⁺ facies with downstream Na⁺–Cl⁻ enrichment. The EWQI classified &gt; 50% of samples as ‘very poor’, with deterioration more pronounced in the post-monsoon. Together, these findings highlight a sustainability paradox that sacred glacier-fed headwaters, commonly treated as pristine baselines in policy frameworks, already carry detectable anthropogenic signals, with implications for monitoring and governance aligned with Sustainable Development Goal 6 (Clean Water and Sanitation).</p>