Water resources and the ecosystem are significantly affected by changes in land use and land cover (LULC). It is essential to estimate the effects of change in LULC on the hydrology of the river basin and understand its mechanism. The main objective of this study is to analyze the effect of change in land use and land cover on the hydrological regime of the Teesta River basin using the comprehensive Soil and Water Assessment Tool (SWAT) model. Calibration and validation were carried out using the observed discharge data on the monthly time scale. The model showed good performance with R2 = 0.74, Nash-Sutcliffe Efficiency (NSE) = 0.63, and Kling-Gupta Efficiency (KGE) = 0.58 during the calibration period and R2 = 0.75, NSE = 0.69, and KGE = 0.66 during the validation period using the Sequential Uncertainty Fitting algorithm. The main contribution to the water yield arises from the northern part of the basin in the Himalayan ranges, which is covered with glaciers, forest, and scrubland. Due to changes in LULC in the past decade, a severe spatial and temporal shift was observed in the water balance components at the sub-basin scale. An increase in the surface runoff in the upper part of the catchment due to the melting of glaciers and the conversion of forest into agricultural fields may lead to an increase in events like flooding and landslides in the low-lying regions in the basin.