The Yangtze River Economic Belt (YREB) is an important part of China’s “two screens and three belts” strategic ecological security barrier, and the urban agglomeration along the YREB is the core of its economic development. However, it has suffered the most from frequent and severe flood disasters that were affected by torrential rains, urbanization, and human activities, with climate change intensifying the potential occurrence of flood disasters in this area. Based on the CMIP6 climate data, this study constructed a flood risk assessment index system and assessed the temporal and spatial changes of the flood risk in the YREB during 2020–2050 under four shared socioeconomic pathways (SSP) scenarios, including SSP126, SSP245, SSP370, and SSP585. From the perspective of temporal change, the results showed that at the grid level, the area of middle-low risk (0.55 < R ≤ 0.65) accounted for 60% of the total area of the YREB and area of high-risk (R > 0.85) fluctuated first and then decreased under the four scenarios, with the area of high-risk being largest in the future under the SSP585 scenario. Specifically, at the city level, around half of the cities in the YREB had faced high flood risk and the risk showed an increasing trend during 2020–2050 under the SSP370 scenario. From the perspective of spatial change, the flood risk of the YREB presented a spatial pattern of low in the west and high in the east, with high risk mainly concentrated in the cities in the lower reaches of the YREB and also Chongqing and Sichuan. Compared with SSP126 and SSP245 scenarios, it showed that high-risk areas were larger under high emission scenarios SSP370 and SSP585, which were mostly concentrated in middle and lower reaches of the YREB and the cities of Chongqing and Chengdu during 2020–2050. Especially, flood risk showed an increasing trend in the middle and lower reaches of the YREB during 2020–2050, and the regions with high vulnerability would have greater socio-economic losses. The finding would provide scientific support for resilience improvement, risk reduction and management, and formulating policies to achieve green and sustainable development in the YREB.