Vegetation coverage in the upper reaches of the Yangtze River is very important to the ecological balance in this area, and it also has an impact on the inflow runoff and sediment transport processes of the Three Gorges Reservoir. Based on the normalized vegetation index data (NDVI) with 250 m resolution in the upper reaches of the Yangtze River, annual runoff, sediment transport, land use, meteorology, and other data—and by using the methods of Sen + Mann–Kendall trend analysis, partial correlation analysis, and Hurst index—this paper analyzes the temporal and spatial variation characteristics, driving factors, and the influence on the water and sediment inflow processes of the Three Gorges Reservoir in each sub-basin in the upper reaches of the Yangtze River. The results show that (1) NDVI in the upper Yangtze River showed a fluctuating upward trend from 2001 to 2022, and the overall vegetation cover continued to increase, showing a spatial pattern of low in the west and high in the east. At the same time, the runoff volume of the upper reaches of the Yangtze River did not show a significant upward trend from 2006 to 2022, while the sand transport decreased significantly; (2) Among the NDVI-influencing factors in the upper reaches of the Yangtze River, the area driven by the land use factor accounts for about 43% of the whole study area, followed by precipitation; (3) Precipitation significantly affected runoff, and NDVI was negatively correlated with sand transport in most of the watersheds, suggesting that improved vegetation could help reduce sediment loss. In addition, the future trend of vegetation change was predicted to be dominated by improvement (Hurst > 0.5) based on the Hurst index, which will provide a reference for the NDVI change in the upper Yangtze River and the prediction of sediment inflow to the Three Gorges Reservoir.