Climate change in the 21st century over China and its different sub-regions is investigated in the study, based on the ensemble of a set of dynamical downscaling experiments over East Asia. The model employed in the experiments is the International Center for Theoretical Physics’ Regional Climate Model, version 4 (RegCM4), at 25-km grid spacing, driven by five different CMIP5 (phase 5 of the Coupled Model Intercomparison Project) global models under the Representative Concentration Pathways RCP4.5 and RCP8.5. The model version used was customized for better performance over the region. Ten sub-regions of China were defined, with consideration paid to local economic and societal developments, vulnerability of ecosystems, and sensitivity to future climate changes. A substantial warming in the future in China is projected, and this warming is more pronounced over the Tibetan Plateau during DJF (December-January-February) and Northwest China (where dry climate prevails) during JJA (June-July-August). A broad increase in temperature extreme indices—Namely, TXx (annual maximum daily maximum surface air temperature) and TNn (annual minimum daily minimum surface air temperature)—is reported, along with increased mean temperature. The results suggest more frequent and intense heat waves in the warm seasons, and thus more risks in terms of human health and mortality, over the sub-regions of Beijing-Tianjin-Hebei, the Yangtze Delta, the Guangdong-Hong Kong-Macao Greater Bay Area, and the Cross-Taiwan Strait Coasts, with their dense cities and populations. Meanwhile, the warming over the Tibetan Plateau may lead to degradation of frozen soil and glacial melt, and thus a greater frequency of related geological hazards, while increased evapotranspiration following the warming over the Arid and Semi-arid Northwest and Losses Plateau sub-regions may worsen the situation with respect to water resource shortages. Precipitation change in DJF shows a prevailing increase in northern China, with good agreement among the ensemble members. The increase is largest in the Northwest China sub-region. In southern China, small changes with a slight decrease in the southern part of the Yunnan-Guizhou Plateau are found. In JJA, precipitation increases over western China, the northern part of Northeast China, and the Yellow-Huai River basins, and shows small changes over other areas. A general increase in the precipitation extreme index (RX1day, the annual maximum 1-day precipitation) is found over the whole country, indicating more extreme precipitation events in the future. For the CDD index (the largest number of consecutive days when the daily precipitation amount is less than 1 mm), a general increase in the north and a decrease in the south are found. Regarding the increases of heavy precipitation events, the Arid and Semi-arid Northwest and Losses and Tibetan Plateau sub-regions, with their fragile ecosystems, may experience relatively more landslide and debris flow events; while over the more populated sub-regions, special concern is needed with respect to the likely greater frequency and more intense nature of flooding and urban-flooding events. Quantitatively, the increases in annual mean temperature, TXx, and TNn in the mid-21st (2041–2060) century relative to the present day (1986–2005) over the whole of China under RCP4.5/RCP8.5 are 1.6/2.2°C, 1.7/2.2°C, and 1.9/2.7°C, respectively. For precipitation, RX1day, and CDD, the values of change are 4%/5%, 9%/12%, and both around −2 d, respectively. The changes become more pronounced with time. By the end of the 21st century (2081–2098), under the higher scenario of RCP8.5, the changes in annual mean temperature, TXx, TNn, precipitation, RX1day and CDD are 4.6, 4.7, 5.5°C, 12%, 25%, and −4 d, respectively. Finally, the deficiencies and uncertainties that remain in projecting the future climate over the region are also outlined and discussed in the paper.