The Chaohu Lake Basin (CLB) is the main flow area of the Yangtze River–Huaihe River Water Transfer Project in Central China. It is important to quantitatively evaluate the water resources in the CLB and predict their response to future climate change. This study simulated and calibrated the water yield in the CLB from 2000 to 2019 based on InVEST. We also analyzed the influence factor on the water yield and predicted the water yield in future years with CMIP6 data. The results demonstrate that: (1) The InVEST water production module had good applicability in this study region. There was a strong linear relationship between the simulated water yield and the observed surface runoff (y = 1.2363x − 8.6038, R2 = 0.868, p < 0.01); (2) The explanatory percentage of interaction between precipitation and land use/land cover for water yield in 2001, 2008, and 2016 reached 71%, 77%, and 85%, respectively, which were the two dominant factors affecting water yield in the CLB; and (3) The average annual water yield in the CLB increased under the SSP2-4.5, SSP3-7.0, and SSP5-8.5 future scenarios with increasing precipitation, increased with 71%, 139.8%, and 159.5% in 2100 compared with 2040, respectively. The overall trend of water production decreased with increases in carbon emission intensity.