Poyang Lake, the largest freshwater lake in China, and its surrounding sub-basins have suffered frequent floods and droughts in recent decades. To better understand and quantitatively assess hydrological impacts of climate change in the region, this study adopted the Statistical Downscaling Model (SDSM) to downscale the outputs of a Global Climate Model (GCM) under three scenarios (RCP2.6, RCP4.5 and RCP8.5) as recommended by the fifth phase of the Coupled Model Inter-comparison Project (CMIP5) during future periods (2010–2099) in the Poyang Lake Basin. A semi-distributed two-parameter monthly water balance model was also used to simulate and predict projected changes of runoff in the Ganjiang sub-basin. Results indicate that: 1) SDSM can simulate monthly mean precipitation reasonably well, while a bias correction procedure should be applied to downscaled extreme precipitation indices (EPI) before being employed to simulate future precipitation; 2) for annual mean precipitation, a mixed pattern of positive or negative changes are detected in the entire basin, with a slightly higher or lower trend in the 2020s and 2050s, with a consistent increase in the 2080s; 3) all six EPI show a general increase under RCP4.5 and RCP8.5 scenarios, while a mixed pattern of positive and negative changes is detected for most indices under the RCP2.6 scenario; and 4) the future runoff in the Ganjiang sub-basin shows an overall decreasing trend for all periods but the 2080s under the RCP8.5 scenario when runoff is more sensitive to changes in precipitation than evaporation.