In this paper we focus on the model setup scheme for medium-size watershed with high resolution, multi-site calibration, and present results on the possible changes of the Minija River in flow, sediment load, total nitrogen (TN), and total phosphorus (TP) load in the near-term (up to 2050) and long-term (up to 2099) in the light of climate change (RCP 4.5 and RCP 8.5 scenarios) under business-as-usual conditions. The SWAT model for the Minija River basin was setup by using the developed Matlab (SWAT-LAB) scripts for a highly customized watershed configuration that addresses the specific needs of the project objective. We performed the watershed delineation by combining sub-basin and hillslope discretization schemes. We defined the HRUs by aggregating the topographic, land use, soil, and administrative unit features of the area. A multisite manual calibration approach was adopted to calibrate and validate the model, achieving good to satisfactory results across different sub-basins of the area for flow, sediments and nutrient loads (TP and TN). After completing the climate change scenario calculations, we found that a net decrease of flow (up to 35%), TN (up to 34%), and TP (up to 50%) loads are projected under both scenarios. Furthermore, we explored the changes in the streamflow composition and provide new insight on the reason of projected nutrient load decrease.