Five General Circulation Model (GCM) climate projections under the RCP8.5 emission scenario were used to drive the Variable Infiltration Capacity (VIC) hydrologic model to investigate the impacts of climate change on hydrologic cycle over continental China in the 21st century. The bias-corrected climatic variables were generated for the Fifth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC AR5) by the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP). Results showed much larger fractional changes of annual mean Evapotranspiration (ET) per unit warming than the corresponding fractional changes of Precipitation (P) per unit warming across the country, especially for South China, which led to a notable decrease of surface water variability (P-E). Specifically, negative trends for annual mean runoff up to −0.33%/year and soil moisture trends varying between −0.02% to −0.13%/year were found for most river basins across China. Coincidentally, interannual variability for both runoff and soil moisture exhibited significant positive trends for almost all river basins across China, implying an increase in extremes relative to the mean conditions. Noticeably, the largest positive trends for runoff variability and soil moisture variability, which were up to 0.41%/year and 0.90%/year, both occurred in Southwest China. In addition to the regional contrast, intra-seasonal variation was also large for the runoff mean and runoff variability changes, but small for the soil moisture mean and variability changes. Our results suggest that future climate change could further exacerbate existing water-related risks (e.g., floods and droughts) across China as indicated by the marked decrease of surface water amounts combined with a steady increase of interannual variability throughout the 21st century. This study highlights the regional contrast and intra-seasonal variations for the projected hydrologic changes and could provide a multi-scale guidance for assessing effective adaptation strategies for China on a river basin, regional, or as a whole.