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The main objective of this study was to assess the hydrological response of the Choke mountain range to land use dynamics. Two watersheds, Muga and Suha watersheds, were selected for detailed evaluation and analysis. The study was conducted using integrated applications of remote sensing and the Soil Water Assessment Tool (SWAT). The SWAT model was calibrated using Sequential Uncertainty Fitting (SUFI-2) algorithm in SWAT-CUP. Decadal land use maps (1985, 1995, and 2005) were used to simulate the hydrological responses. Simulated model results showed that over the past two decades (1985–2004), the total annual surface and lateral streamflows in the watershed increased at a rate of 1.2 mm/year and 0.57 mm/year, whereas the annual total groundwater flow and percolation in the basin decreased at a rate of 1.6 mm/year and 1.77 mm/year respectively. The decrease in the streamflow was more pronounced during the dry season (October to May), for which statistically significant declines of the base flow or the low flow at a rate of 0.37 m3/year and 0.73 m3/year in the Muga and Suha watersheds, respectively, were found. In the wet season (June to September), the peak flow has increased by 50% in Muga and 94% in Suha watersheds. Results of this study showed that the SWAT model can be an effective and useful tool for the assessment of response of watersheds to land use alterations.