In Taiwan, non-point source (NPS) pollution is one of the major causes of the impairment of surface waters. NPS pollutants, which are associated with stormwater runoff from agricultural land uses can be quite diffuse and difficult to treat. The I-Liao Creek Basin, located in southern Taiwan, flows through approximately 90-km and drains towards the Kaoping River. It is one of the major sub-basin in the Kaoping River watershed, which is the largest and the most intensively used watershed in Taiwan. Field investigation results indicate that the main water pollution sources in the I-Liao Creek Basin are domestic wastewater and NPS pollutants from agricultural activities. In this study, an Integrated Watershed Management Model (IWMM) was applied for simulating the water quality in the I-Liao Creek watershed. The model includes a global atmosphere module, a land module, a human impact module, a canopy module, and a global ocean module. Those modules can be linked and managed by a graphic user-interface. The model was calibrated and verified with field data, and was used to investigate potential NPS pollution management plans. Moreover, the Storm Water Management Model (SWMM) was used to verify the accuracy of the simulated results of flow and water qualities. Results from this study show that geographical information system (GIS) is an important mean for land-use identification and waste load estimation in the catchment. Linking the information of land utilization with the NPS pollution simulation model may further provide essential information of pollution potential of NPS pollution for all sub-regions in the river basin. Results and experience obtained from this study will be helpful in designing the watershed management and NPS pollution control strategies for other similar river basins.