The Pisha sandstone area is broken in topography, with little precipitation and mainly rainstorm, the ecological environment in the area is harsh. It is of great theoretical significance for regional vegetation construction to study the dynamic change of vegetation and explore the response characteristics of vegetation coverage to environmental factors. Based on the normalized difference vegetation index (NDVI) from 1999 to 2018, this study analyzed the spatio-temporal change characteristics of vegetation coverage in the Pisha sandstone area. In addition, the geodetector was used to analyze the influence of different environmental factors on the change of vegetation coverage, then we determined the most suitable range and type of each factor to promote vegetation growth. The results show that:1) In the past 20 years, the average vegetation coverage in the Pisha sandstone area was 42.3%. On the time scale, the regional vegetation coverage had an increasing trend from 1999 to 2018, with an average increase of 0.086/10 a. On the spatial scale, the vegetation coverage presents a distribution characteristic of decreasing from southeast to northwest. The vegetation coverage of the three areas changes from large to small in order of soil-covered Pisha sandstone area, sand-covered Pisha sandstone area, and bare Pisha sandstone area. 2) In the past 20 years, the overall improvement of vegetation coverage in the Pisha sandstone area is greater than the degraded area. About 45.5% vegetation coverage of the regional area has increased obviously, mainly in the eastern part of the Pisha sandstone area whereas the significantly reduced areas were scattered in the middle of the bare area. The future trend of vegetation coverage in the Pisha sandstone area will be dominated by continuous improvement, accounting for 50.5% of the total area, mainly distributed in the southern soil-covered Pisha sandstone area. Although the vegetation in this area is showing an overall trend of improvement, it still faces greater challenges. About 41.6% of the vegetation is at risk of changing from improvement to degradation. 3) Precipitation, soil moisture and temperature are the dominant environmental factors that affect the spatial distribution of vegetation coverage in the region, while the slope and aspect have the weakest explanatory power for vegetation coverage. The interaction among environmental factors is dominated by a two-factor enhancement trend. As the dominant climate factor in the spatial distribution of vegetation coverage in this region, precipitation has the greatest influence on vegetation coverage under the interaction with other environmental factors.