The Yellow River Basin is located in the arid and semi-arid area of China, which ecological environment is fragile. The researches about vegetation index changes and its response to climate factors were significant to the ecological construction of the region. Based on the MODIS normalized difference vegetation index (NDVI), enhanced vegetation index (EVI) and meteorological data, we mainly used Maximum Value Composite (MVC), trend analysis, and partial correlation analysis to explore the characteristics of the spatio-temporal changes of vegetation cover and driving mechanism of climatic factors in the Yellow River Basin from 2000 to 2018. At the same time, the differences between the NDVI and EVI reflected variations of vegetation and their responses to climatic factors were discussed. Results showed that the temporal change rate of NDVI and EVI in the Yellow River Basin increased at 0.059/10 a and 0.038/10 a, respectively. In terms of space, the main areas significantly improved, accounting for 77.13% and 75.27% of the area, respectively. Most of them were distributed at 1000-1500 m elevations, and the middle reaches have improved well. The improvement rate of forest land was higher than that in other areas. The degraded areas were relatively rare and mainly distributed in the northwestern Bayan Qula Mountain, Xining City, Yinchuan City, Baotou City, Hohhot City, Taiyuan City, Xi'an City, the Guanzhong Basin and the surrounding areas of Luoyang City. The degradation rate of construction land was higher compared with other areas. During the growing season, the change of vegetation index (VI) was positively correlated with air temperature and precipitation, the lag time of air temperature in the VI was one month, while in precipitation the lag time were three months. Among them, grassland showed the most significantly positive correlation. There was a negative correlation between radiation and vegetation index, and the time lag was about 3 months, among which the most relevant area was in forest land. At the significant level of 0.05, the precipitation and radiation driven the vegetation change during the growing season in the Yellow River Basin. On the whole, precipitation had a great influence on the change of vegetation in this area. In terms of temporal and spatial changes, the NDVI was more sensitive to vegetation change than EVI, and had a higher correlation with precipitation and radiation in the Yellow River Basin.