The hydrological cycle is altered by climate change and human activities, amplifying extreme precipitation and heightening the flood risk regionally and globally. It is imperative to explore the future possible alterations in flood risk at the regional scale. Focusing on the Hanjiang river basin (HRB), this study develops a framework for establishing a scientific assessment of spatio-temporal dynamics of future flood risks under multiple future scenarios. In this framework, a GCMs statistical downscaling method based on machine learning is used to project future precipitation, the PLUS model is used to project future land use, the digitwining watershed model (DWM) is used to project future runoff, and the entropy weight method is used to calculate risk. Six extreme precipitation indices are calculated to project the spatio-temporal patterns of future precipitation extremes in the HRB. The results of this study show that the intensity (Rx1day, Rx5day, PRCPTOT, SDII), frequency (R20m), and duration (CWD) of future precipitation extremes will be consistently increasing over the HRB during the 21st century. The high values of extreme precipitation indices in the HRB are primarily located in the southeast and southwest. The future annual average runoff in the upper HRB during the near-term (2023–2042) and mid-term (2043–2062) is projected to decrease in comparison to the baseline period (1995–2014), with the exception of that during the mid-term under the SSP5-8.5 scenario. The high flood risk center in the future will be distributed in the southwestern region of the upper HRB. The proportions of areas with high and medium–high flood risk in the upper HRB will increase significantly. Under the SSP5-8.5 scenario, the area percentage with high flood risk during the future mid-term will reach 24.02%. The findings of this study will facilitate local governments in formulating effective strategic plans for future flood control management.