Non-point source (NPS) pollution is a primary cause of water pollution in the Saemangeum watershed in South Korea. The changes in NPS pollutant loads in the Saemangeum watershed for an 81-year period (2019–2099) were simulated and analyzed by applying the soil and water assessment tool. Six climate model (BCC-CSM1–1, CanESM2, GFDL-ESM2G, HadGEM2-CC, INM-CM4, and MIROC-ESM) outputs using representative concentration pathway (RCP) scenarios (RCP 4.5 and RCP 8.5) were obtained from the South Korean Asia-Pacific Economic Cooperation (APEC) Climate Center. Simulated streamflow and water quality were evaluated using the Nash–Sutcliffe efficiency (NSE) index and coefficient of determination (R2). The model satisfactorily simulated streamflow with positive NSE values and R2 > 0.5. Based on two climate change scenarios (RCP 4.5 and RCP 8.5), gradual increases of 70.9 to 233.8 mm and 1.7 to 5.7 °C in annual precipitation and temperature, respectively, are likely for two time periods (2019–2059 and 2060–2099). Additionally, the expected future average annual and monthly streamflow, sediment, and total phosphorus showed changes of 5% to 43%, 3% to 40%, and −55% to 15%, respectively, whereas the expected future average annual and monthly total nitrogen showed decreases of −5% to −27%. Future NPS pollutant loads in the Saemangeum watershed should be managed according to different climate change scenarios.