Abstract: Hetao irrigation district, the largest self-flowing irrigation district in Asia, faces a serious agricultural non-point source (NPS) pollution problem resulting from its high-input and high-output farming practices. A large amount of nitrogen is transported progressively into the main drainage canal via agricultural return flow. This study utilized the digital elevation model (DEM) preprocessed by remote sensing data within the Soil and Water Assessment Tool (SWAT) model to explicitly define the watershed's drainage network and delineate the sub-basins. The model was used to analyze the changes in the cumulative loss of TN load in the basin under different climate scenarios and best management practices (BMPs). The results showed that the SWAT model constructed using the treated DEM data could accurately simulate the drainage ditch system in the basin, demonstrating a 98% spatial agreement between the model-generated drainage system and the real drainage system. Calibrating the watershed runoff and total NPS load based on this could accurately simulate the irrigation area under human intervention. The combination of a 20% reduction in fertilization and a 10% reduction in irrigation was most effective in reducing TN load. The reduction rates of accumulated TN load loss in the watershed under historical and projected climate scenarios were 6% and 8%, respectively. Climate change had a significant impact on the cumulative loss of TN load in the southern region of Hetao irrigation district's main drainage canal. The load showed a trend of gradual accumulation from west to east, peaking at the main drainage canal. Climate change increased the cumulative loss of TN load in the irrigation area by nearly 9 times, and significantly increased the frequency and intensity of extreme rainfall events in the future, resulting in the accumulation of more than 60% of the nitrogen load in the whole basin at the main drainage canal. The model can serve as a valuable tool for the source pollution control under the climate change scenario in Hetao irrigation district and offer an early warning system for dealing with the risk of NPS pollution outbreak caused by climate change.