Identifying the contributions of climate- and human-induced impacts on runoff change have aroused broad attention globally in the hydrological cycles and water resource management. However, a systematic quantitative assessment of the impact of climate changes and human activities on historical and future runoff changes in the upper Yangtze River (UYR) and the effects of runoff variation on stormflow characteristics (e.g., annual runoff distribution) remain unclear. Here, we quantified runoff variations and simulated runoff in the UYR using the Soil and Water Assessment Tool (SWAT) hydrologic model and statistical methods. Our main findings include: (1) climate variability played a dominant role in runoff decline in the UYR from 1972 to 2016 (Slope: -0.10 mm/a, P-value < 0.05), accounting for 43.34 % of the total decrease, while anthropogenic activities accounted for 4.82 %; (2) runoff in the upcoming period of 2020-2059 under RCP 2.6, RCP 4.5, and RCP 8.5 will increase significantly (P-value < 0.05) at a rate of 0.14 mm, 0.13 mm, and 0.27 mm per year, respectively; (3) water yield and hydrological drought are all projected to decrease in the entire UYR, but flood frequency will increase under the 1.5 degree celsius and 2.0degree celsius global warming. This study provides a new perspective for understanding the status of water resources in the UYR and offers great implications for flood control and effective water resources management over the UYR in the future.