Understanding the historical and future changing characteristics of key climatic variables and runoff in 10 major river zones in China is essential for water resources evaluation and management. To this end, the historical and future changing trends of key hydrometeorological variables, including precipitation, potential evapotranspiration, and runoff were analyzed in detail for each water zone across China. The climate elasticity method was also established to quantify the impacts of climate change and human activities on historical runoff variations. The results indicate that the characteristics and causes of runoff variations in China were generally spatially heterogeneous. The runoff in water-scarce river basins of northern China decreased significantly during the period of 1961-2018, variations of which were more sensitive to human activities. For southern water zones in China, the runoff showed no significant trend and climate change was the main influencing factor. On basis of 9 Coupled Model Intercomparison Project Phase 6 (CMIP6) climate model ensemble simulations under three different shared socioeconomic pathways (ssp126, ssp245 and ssp585), the future runoff in 10 typical basins of the water zones were projected and the results suggested an increasing trend of runoff over China, thanks to increasing precipitation in the rest 21 century. While under ssp585, the rising air temperature tends to evaporate more water and offset the effect of precipitation increase to some extent, resulting in that the increments of runoff under ssp585 are not necessarily greater than those under ssp245 and ssp126. Overall, our study could be used as a basis to support climate adaptation strategies and policies to cope with future water resources conditions.