The water quality of rivers is deteriorating due to human interference. It is essential to understand the relationship between human activities and land use types to assess the water quality of a region. GIS is the latest tool for analyzing this spatial correlation. Land use land cover, and change detection are the best illustration for showing the human interactions with land features. This study assessed water quality index of the upper Ganges River near Haridwar, Uttarakhand, and spatially correlated it with changing land use to reach a logical conclusion. In the upper course of Ganges, along a 78-km stretch from Kaudiyala to Bhogpur, water samples were collected from five stations. For water quality index, physicochemical parameters like pH, EC, DO, TDS, CaCO3−, CaCO3, Cl−, Ca2+, Mg2+, Na+, K+, F−, Fe2+ were considered. The results of the spatial analysis were evaluated through error estimation and spatial correlation. The root mean square error between spatial land use and water quality index at the selected sampling sites was estimated to be 0.1443. The spatial correlation between land use change and site-wise differences in water quality index also showed a high positive correlation, with R2 = 0.8455. The degree of positive correlation and root mean square error strongly indicated that the water quality of the river in the upper course of the Ganges is highly impacted by human activities.