Vegetation coverage is an important indicator for evaluating regional environmental quality. Based on MODIS NDVI and DEM data collected for the upper reaches of the Ganjiang River Basin, China, this study used trend analysis, coefficient of variation, Hurst index, and linear regression to analyze the temporal and spatial evolution of vegetation coverage and its relationship with terrain factors in the basin during the years 2000–2020. The vegetation coverage in the study area showed a fluctuating increasing trend at a rate of 5%/10y, and an increasing trend with increasing elevation. The maximum vegetation coverage was identified in the elevation zone of 750–1,000 m, with an average of 83.54%. Vegetation coverage also showed an increasing trend with increasing slope. The maximum vegetation coverage was up to 82.22% in the slope zone of ≥25°. There were no significant differences among the distributions of vegetation coverage in different aspects because the terrain in the study area is not rugged enough to form barriers against sunlight. The vegetation coverage was relatively stable in the study area, with an average coefficient of variation of 14.8%. Hurst analysis showed that the anti-sustainability effect of vegetation change was stronger than that of sustainability, and weak anti-sustainability was dominant. The effects of human activities mainly concentrated in the areas of low elevation and small slopes less than 2°where cities and towns are located. The findings can provide a scientific basis for the management of regional ecosystems in the future.