Abstract: Climate change has profoundly altered hydrological processes and the spatiotemporal distribution of water resources at both regional and global scales. The Yangtze River Basin, as the largest river basin in China, is particularly sensitive to climate-driven changes in precipitation patterns, temperature regimes, and evapotranspiration dynamics. Accurately projecting future runoff trends within the basin therefore carries significant scientific value for the sustainable development and rational allocation of regional water resources, as well as for informing long-term water security strategies and disaster risk management policies. This study employs the RCCC-WBM (Research Center for Climate Change - Water Balance Model) to construct a spatially distributed runoff simulation framework encompassing 14 sub-units across the entire Yangtze River Basin, capturing the pronounced spatial heterogeneity in climate, topography, and hydrological response characteristics across the basin. The model was rigorously calibrated and validated against long-term observed streamflow records, with the Nash–Sutcliffe Efficiency (NSE) coefficient exceeding 0.9 for total basin-wide runoff simulation during both the calibration and validation periods, confirming the model's high reliability and strong capability to reproduce observed runoff dynamics. To drive future runoff simulations, the study incorporates ensemble-mean climate forcing data from 19 General Circulation Models (GCMs) participating in the sixth phase of the Coupled Model Intercomparison Project (CMIP6). Four Shared Socioeconomic Pathway (SSP) scenarios were selected to represent a broad range of plausible future greenhouse gas emission trajectories: the low radiative forcing pathway (SSP1-2.6), the intermediate radiative forcing pathway (SSP2-4.5), the medium-to-high radiative forcing pathway (SSP3-7.0), and the high radiative forcing pathway (SSP5-8.5). Together, these scenarios provide a robust multi-scenario framework for assessing the sensitivity of basin hydrology to varying levels of anthropogenic climate forcing over the projection period from 2015 to 2100. The study yields four principal findings. (1) Under all four SSP scenarios, both mean annual temperature and total annual precipitation across the Yangtze River Basin exhibit statistically significant upward trends throughout the 21st century. The magnitude of warming and precipitation increase scales consistently with the level of radiative forcing, indicating a warmer and wetter future for the basin with important implications for runoff generation, flood frequency, and water availability. (2) The RCCC-WBM model demonstrated robust performance in simulating the hydrological regime of the Yangtze River Basin. NSE values exceeding 0.9 during both the calibration and validation periods confirm a high level of simulation accuracy, lending strong confidence to the reliability of subsequent future projections. (3) Future annual runoff across the Yangtze River Basin is projected to increase significantly under all four scenarios relative to the baseline reference period of 1995–2014. Mean annual runoff is projected to increase by approximately 2.4% to 9.6% by the 2035 horizon year, 3.9% to 13.5% by the 2050 horizon year, and 11.1% to 16.6% by the 2080 horizon year. The progressively widening inter-scenario range toward the end of the century reflects growing divergence between low- and high-emission futures, highlighting that the extent of future runoff increase is critically dependent on global emission trajectories. (4) Intra-annual runoff across all seasons also exhibits significant increasing trends, with summer contributing most substantially to the total annual runoff increase, likely driven by intensified monsoon precipitation and accelerated glacial melt under warming conditions. Spatially, projected runoff increments display a downstream-decreasing gradient along the mainstream Yangtze River, with the upper reaches experiencing the largest absolute increases. The Two Lakes Basin—encompassing the Dongting Lake and Poyang Lake sub-basins—exhibits the smallest projected runoff increments among all sub-units, suggesting that future hydrological benefits may be unevenly distributed across the basin. The findings of this study provide important scientific evidence for climate change impact assessment, long-term water resource strategic planning, integrated flood and drought risk management, and the formulation of adaptive disaster prevention strategies in the Yangtze River Basin, contributing to evidence-based water governance under an increasingly uncertain climate future.