The Yangtze River Basin is an important ecological barrier in China. Scientific understanding of the spatial-temporal variations of vegetation coverage and associated driving forces in the Yangtze River Basin are of great significance and application value for the effective development of ecological engineering construction for Yangtze River Basin. Based on MODIS-NDVI data and meteorological data from 2000 to 2019, this study investigated the spatio-temporal variation and change characteristics of vegetation coverage in the Yangtze River Basin during past 20 years, and the driving factors of vegetation coverage in the study area was explored by using the methods of Theil-Sen median trend analysis, Mann-Kendall test, coefficient of variation, partial correlation analysis and residual analysis. The results are as follows:(1) in terms of time scale, the NDVI in the growth season of the Yangtze River Basin showed a fluctuating growth trend, and the significantly improved area was larger than the degraded area; (2) In terms of spatial distribution, the spatial distribution pattern of vegetation coverage appears as characteristics of "high in the middle and low in the east and west" in the Yangtze River Basin. The multi-year average value of the NDVI in the growing season is 0.6164, showing a high vegetation coverage state; (3) In terms of change trend, the vegetation growth area is larger than the decrease area, which is specifically expressed as "the central region is stronger than the east, and the east is stronger than the west"; (4) In terms of change stability, the coefficient of variation is between 0.0104 and 1.3199, showing the characteristics of "low in the middle, high in the east and west, high and low fluctuations in local areas of east and west, and obviously regional differences" for the spatial variation of stability; (5) In terms of influencing factors, the change of vegetation cover in the Yangtze River Basin was affected by both climate and precipitation. In most regions, the change of NDVI in the growing season was mainly driven by climate, while in some regions, it was driven by the combination of natural factors and human factors. Residual analysis showed that human activities had a positive effect on vegetation cover in the Yangtze River Basin.