The River Ganges being the most sacred river and lifeline to millions of Indians in serving their water requirements is facing excessive threat of pollution. Under various river management and conservation strategies for its protection, the assessment of water quality of its main tributary Ramganga River is lacking. This study focuses on assessment of physicochemical and heavy metal pollution of the Ramganga River by application of multivariate statistical techniques. Sampling of Ramganga River at sixteen sampling sites was carried out in three seasons (summer, monsoon and winter) of 2014. The collected water samples were analyzed for physicochemical parameters and heavy metals. Results from cluster analysis (CA) of the data divided the whole stretch of the river into three clusters as elevation from 1304 to 259 m as less polluted, from 207 to 154 m as moderately polluted and from elevation 154 to 139 m as high-polluted stretches with anthropogenic as main sources of pollution in high-polluted stretch. Principal component analysis of the seasonal dataset resulted in three significant principal components (PC) in each season explaining 72–8% of total variance with strong loadings (>0.75) of PC1 on fluoride (F−), chloride (Cl−), sodium (Na+), calcium (Ca2+), magnesium (Mg2+), bicarbonate (HCO3−), total dissolved solids and electrical conductivity. Temporal variation by one-way ANOVA (Analysis of Variance) showed significant seasonal variation was in the pH, chemical oxygen demand, biochemical oxygen demand, turbidity, HCO3−, F−, Zn, cadmium (Cd) and Mn (p < 0.05). Turbidity showed approximately a twofold increase in monsoon season due to rainfall in the catchment area and subsequent flow of runoff into the river. Concentration of HCO3−, F− and pH also showed similar increase in monsoon. The concentration of Zn, Cd and Mn showed an increasing trend in summers compared to monsoon and winter season due to dilution effect in the monsoon season and its lasting effect in winters.