[Objective] As the core water source area of the Middle Route of the South-to-North Water Diversion Project, runoff variations in the Danjiang River Basin directly influence water transfer capacity and source water security. Current research primarily relies on manually defined meteorological parameters, limiting scenario diversity and resulting in an insufficient scientific basis, yet studies on future runoff evolution remain scarce. This study aims to analyze the impact of future climate change on runoff in the Danjiang River Basin to provide a scientific basis for water resource management and the operation of the South-to-North Water Diversion Project. [Methods] This study first used the CN05.1 meteorological dataset and observed daily runoff data to construct and calibrate a SWAT hydrological model, simulated runoff variations during the historical period, and verified the model accuracy. On this basis, future meteorological data from six high-performing global climate models (GCMs) under three Shared Socioeconomic Pathways (SSP1-2.6, SSP2-4.5, and SSP5-8.5) of the Coupled Model Intercomparison Project Phase 6 (CMIP6) were bias-corrected using the Delta method to better represent the climatic characteristics of the Danjiang River Basin. Meanwhile, the PLUS model was applied to simulate two land use change scenarios to reflect potential future land use dynamics. The bias-corrected climate data were then combined with different land use scenarios and input into the SWAT model to simulate the spatiotemporal evolution of future runoff. [Results] (1) The SWAT model demonstrated excellent performance in simulating monthly streamflow at Jingziguan and Danfeng stations, with R² values exceeding 0.9 and NSE values above 0.8. The GCMs accurately captured the evolution patterns of temperature extremes and precipitation in the region, with correlation coefficients exceeding 0.85 for temperature and 0.7 for precipitation. (2) In the future, both temperature and precipitation in the Danjiang River Basin were projected to increase. Across all scenarios, temperature increases followed the pattern: late period>mid period>near period, with the most pronounced change under the high carbon scenario, where the late-period temperature rise reached 7.11 ℃, 2.72 times that under the low carbon scenario. Precipitation generally showed a continuous upward trend, with the largest increase (11.63%) under the low carbon scenario. The fastest increase occurred in summer, while winter precipitation under the low carbon scenario increased by 10.38%. (3) Runoff in the Danjiang River Basin exhibited significant spatiotemporal variability. The annual average runoff shifted from a decrease in the near period to an increase in the far period. Seasonal variations indicated significant increases in spring and winter, and decreases in summer and autumn, with the most pronounced increases in January and December and the most notable decreases in July and September. Spatially, downstream runoff increased markedly, with widespread growth in the mid to far period under the low carbon scenario, and prolonged decreases under the high carbon scenario. [Conclusion] (1) In the near term, the annual average runoff shows a downward trend with frequent fluctuations. Under the medium carbon scenario, the maximum annual runoff reduction reaches 25.32%. The high carbon scenario exhibits 16 abrupt changes during the study period without stable recovery, resulting in coexisting risks of extreme floods and droughts due to long-term runoff variability. (2) In the mid to long term, runoff generally recovers, although significant differences remain among scenarios. Under the low and medium carbon scenarios, runoff increases by up to 20.34%, which supports water supply security for the South-to-North Water Diversion Middle Route Project and meets the water demand of the basin’s ecosystems. In contrast, under the high carbon scenario, runoff increases by less than 1.00%, and supply risks persist. (3) The low carbon scenario is most favorable for the long-term development of the basin, while the high carbon scenario poses the greatest risks. Runoff recovery occurs earliest under the low carbon scenario, ensuring ecological water demand and water security. By contrast, under the high carbon scenario, recovery is slow, and fluctuations are frequent, increasing the probability of extreme droughts or floods.