Climate change has an important impact on water balance and material circulation in watersheds. Quantifying the influence of climate and climate-driven vegetation cover changes on watershed-scale runoff and sediment yield will help to deepen our understanding of the environmental effects of climate change. Taking the Zhenjiangguan Watershed in Sichuan Province, China as a case study, three downscaled general circulation models with two emission scenarios were used to generate possible climatic conditions for three future periods of P1 (2020-2039), P2 (2050-2069) and P3 (2080-2099). Differences in scenarios were compared with the base period 1980-1999. Then, a Normalized Difference Vegetation Index climate factor regression model was established to analyze changes to vegetation cover under the climate change scenarios. Finally, a Soil and Water Assessment Tool model was built to simulate the response of runoff and sediment yield in the three future periods under two different scenarios: only changes in climate and synergistic changes in climate and vegetation cover. The temperature and precipitation projections showed a significant increasing trend compared to the baseline condition for both emission scenarios. Climate change is expected to increase the average annual runoff by 15%-38% compared with the base period, and the average annual sediment yield will increase by 4%-32%. The response of runoff and sediment yield varies in different periods, scenarios, and sub-watersheds. Climate-driven vegetation cover changes have an impact on runoff and sediment yield in the watershed, resulting in a difference of 5.8%-12.9% to the total changes. To some extent, the changes in vegetation cover will inhibit the hydrological impact of climate changes. The study helps to clarify the effects of climate and vegetation cover factors on hydrological variations in watersheds and provides further support for understanding future hydrological scenarios and implementing effective protection and use of water and soil resources.