The Dhansiri River, situated in north-east India, is a transboundary river running through the states of Assam and Nagaland, and forms an important tributary to the Brahmaputra River. Despite the religious and cultural importance of the river, the anthropogenic waste disposed off at the catchment areas has hampered the potability of the once pristine water source for the tribal communities residing along its banks. In order, to understand the seasonal alteration in the water quality and its applicability for different domestic usage, the study emphasized the application of statistical tools and Water Quality Index to monitor the overall health of the river water. Considering the objectives, from three distinct sites (DS1, DS2, and DS3) water samples were collected during winter, spring, summer and autumn in the year 2021-2022. In total, 16 physicochemical properties were evaluated and the parameters like, water temperature, total dissolve solids, electrical conductivity, turbidity, and total alkalinity exhibited a seasonal significant difference at p<0.001. Turbidity and total alkalinity value exceeded the standard permissible limits of Bureau of Indian Standards (2012) and World Health Organisation (2017). The average Water Quality Index was highest in DS3, with the seasonal order: summer (112.61), autumn (90.00), spring (79.88), and winter (69.84). This research suggests that human activities, including urbanization, untreated industrial effluents, agricultural runoff, and improper home waste disposal are key contributors to the degradation of river water. Therefore, it is essential that a robust water resource planning programme be devised by the regional authorities to restore and rejuvenate the deteriorated river.