Abstract: Based on the CN05.1 observation grid data and CMIP6 (Coupled Model Intercomparison Project Phase 6) model simulation data, this study comprehensively evaluated the simulation capability of CMIP6 models for scPDSI (self-calibrating Palmer Drought Severity Index) of China and selected seven model ensembles with relatively good performance to project the change characteristics of scPDSI, runoff, and soil moisture in China in the 21st century. On this basis, this study analyzed the uncertainty in the CMIP6 future projection. The results show that the simulation capability of CMIP6 models for scPDSI over China still needs improvement and the simulation performance of the multimodel ensemble is better than most individual models, but deficiencies remain in temporal and amplitude trends. The temporal trend of scPDSI shows a slightly increasing trend for the SSP1-2.6 and SSP2-4.5 scenarios, with trend values of 0.03 (10 a)⁻¹ and 0.01 (10 a)⁻¹, respectively, and decreasing for the SSP5-8.5 scenario −0.05 (10 a)⁻¹. Soil moisture shows decreasing trends over time: the trend values of the surface soil moisture and total soil moisture are −0.30% (10 a)⁻¹ and −0.26% (10 a)⁻¹ for the SSP5-8.5 scenario, respectively. Runoff shows increasing trends with time: the trend values of the surface runoff and total runoff are 1.76% (10 a)⁻¹ and 3.13% (10 a)⁻¹ for the SSP5-8.5 scenario, respectively. At the end of the 21st century, the annual scPDSI over China generally decreases under SSP5-8.5scenario, changes in soil moisture are generally “high in the North and low in the South”, the downtrend is most significant in the Qinghai–Xizang Plateau region, and the change range of surface soil moisture is bigger than total soil moisture. Runoff tends to rise in most areas, except in Northwest China and Qinghai–Xizang Plateau region, and its change range is bigger with the emission scenarios. The probability density curves of most variables in the 21st century flatten as the emission scenarios increase, so future changes will become more dramatic.