The spatial and temporal variations in the hydrochemistry of the Sutlej river in the Indian Punjab were studied based on water quality parameters analysed during pre- and post-monsoon seasons of the years 2017 and 2018. The grab water samples were collected from the river using stratified random sampling and analysed for pH, electrical conductivity (EC), carbonate (CO3−2), bicarbonate (HCO3−), chloride (Cl−), nitrate (NO3−), total hardness, calcium (Ca+2), sodium (Na+) and potassium (K+) using standard methods. Spatio-temporal variations in the parameters used to evaluate the water quality for irrigation (electrical conductivity (EC), residual sodium carbonate (RSC) and sodium absorption ratio (SAR)) were also studied. In order to rate the composite influence of all the physicochemical parameters, water quality index (WQI) was computed. Spatial variations in WQI for drinking and irrigation purposes were studied using the inverse distance weighted method in GIS. Results showed that the river water was alkaline in nature, HCO3− and Cl− are the major anions, and Ca2+ and Na+ are the cations in the river water during both seasons. The regression analysis of EC with cations and anions showed that the regression coefficient was mainly significant with Ca2+ and HCO3−, irrespective of the season. The concentration of ions was not significantly affected by season, but it was higher along transboundary of the river. Total alkalinity of water was significantly (p < 0.05) higher during pre-monsoon than post-monsoon season. The EC, SAR and RSC values during different seasons showed that > 85% of the water samples were in good categories for irrigation purposes. According to grades of WQI for drinking purposes, the poor WQI was observed in 3.6%, 3.7% and 5.9% of the samples during pre-2017, pre-2018 and post-monsoon 2018, respectively. The poor water quality index for irrigation purposes was observed in 16.7% and 4.7% of the samples during pre-monsoon 2017 and 2018, respectively. The water quality index values for drinking and irrigation were higher (poor water quality) along transboundary of the river. The ratio of Ca2+/Mg2+, (Na+ + K+)/TZ+ and Ca2+ + Mg2+/(Na+ + K+) indicated both carbonate and silicate lithology contribute to hydrochemistry of the river besides anthropogenic factors. Non-metric multidimensional scaling showed that all the samples are of a similar origin across the river including transboundary, whereas cluster analysis resulted in the two main groups: pH and Cl in the one group, and EC along with the remaining cations and anions in the other group during pre-monsoon, but pH in the one group, and EC along with the remaining cations and anions in the other group during post-monsoon. The high concentration of Cl− is a signature of anthropogenic inputs in addition to the contribution of natural factors. These results suggest that the cultivation of crops on the soils along transboundary may cause the transfer of ions through the food chain to human beings affecting their health. Moreover, drinking of river water by inhabitants living along transboundary may affect their health.