Land use and climate change can influence runoff and soil erosion, threatening soil and water conservation in the Cerrado biome in Brazil. The adoption of a process-based model was necessary due to the lack of long-term observed data. Our goals were to calibrate the WEPP (Water Erosion Prediction Project) model for different land uses under subtropical conditions in the Cerrado biome; predict runoff and soil erosion for these different land uses; and simulate runoff and soil erosion considering climate change. We performed the model calibration using a 5-year dataset (2012-2016) of observed runoff and soil loss in four different land uses (wooded Cerrado, tilled fallow without plant cover, pasture, and sugarcane) in experimental plots. Selected soil and management parameters were optimized for each land use during the WEPP model calibration with the existing field data. The simulations were conducted using the calibrated WEPP model components with a 100-year climate dataset created with CLIGEN (weather generator) based on regional climate statistics. We obtained downscaled General Circulation Model (GCM) projections, and runoff and soil loss were predicted with WEPP using future climate scenarios for 2030, 2060, and 2090 considering different Representative Concentration Pathways (RCPs). The WEPP model had an acceptable performance for the subtropical conditions. Land use can influence runoff and soil loss rates in a significant way. Potential climate changes, which indicate the increase of rainfall intensities and depths, may increase the variability and rates of runoff and soil erosion. However, projected climate changes did not significantly affect the runoff and soil erosion for the four analyzed land uses at our location. Finally, the runoff behavior was distinct for each land use, but for soil loss we found similarities between pasture and wooded Cerrado, suggesting that the soil may attain a sustainable level when the land management follows conservation principles.