[Objective] The spatial and temporal variation characteristics of vegetation cover in Yan’an City and its relationship with climate change and human activities were studied in order to provide scientific support for the evaluation of eco-environmental benefits and eco-environmental construction in this area. [Methods] Linear trend analysis, correlation analysis, and residual analysis of MODIS-NDVI and meteorological data were used to determine the spatio-temporal characteristics and influencing factors of vegetation cover change in Yan’an City from 2000 to 2020. The effects of different factors on vegetation cover change and the interaction among them were analyzed by geographic detector. [Results] ① During the past 21 years, NDVI in Yan’an City showed an overall upward trend with a growth rate of 10%/10 yr, which was faster than the average growth rate of vegetation coverage in the Three-North Shelterbelt System. ② The vegetation cover in Yan’an City had been optimized, with 99.64% of the area showing improvement, of which 97.85% was significantly improved, and the proportion of the area showing degradation was very small. ③ Influenced by the distribution of water and heat, Yan’an City exhibited a vegetation distribution pattern of “high in the east and low in the west, high in the south and low in the north”. ④ The correlation coefficient between NDVI and precipitation was significantly larger than the correlation coefficient between NDVI and temperature in this area. The correlation coefficient between NDVI and temperature ranged from -0.60 to 0.70, and the positive correlation area accounted for 47.52% of the total area. The correlation coefficient between NDVI and precipitation ranged from -0.23 to 0.91, and the positive correlation area accounted for 99.62% of the total area. ⑤ The effective implementation of the policy of returning farmland to forest and grass in Yan’an City was the most significant factor in improving vegetation cover, followed by the role of precipitation. The roles of temperature and physical geography were smaller. [Conclusion] Yan’an City is a central city in the hinterland of the Loess Plateau. Vegetation cover there was influenced by climate and human activities. Ecological construction in the future will require knowledge based on the resource availability of different regions, with reasonable participation of human factors, and the use of corresponding control and compensation measures according to local conditions, with a view to achieving the effect of continuous increases in NDVI in Yan’an City and further enhancement of the ecological benefits of Yan’an City.