Vegetation plays a key role in improving the fragile ecological environment of the Loess Plateau. The spatial correlation between normalized difference vegetation index (NDVI) spatial distribution and environmental factors can provide a scientific basis for the high-quality construction of vegetation on the Loess Plateau in the new era. In this study, the spatial correlation between natural environmental factors (climate, topography, soil types and vegetation types) and NDVI from 2000 to 2017 on the Loess Plateau was analyzed by GIS and geographical detector on the premise of eliminating the grid with changes in land use types. The results indicated: (1) from 2000 to 2017, the average annual NDVI on the Loess Plateau ranged from 0.016 to 0.72, which showed a gradually increasing zonal distribution from northwest to southeast, with 50.23% of the areas greater than 0.3. (2) The annual average vegetation NDVI distribution showed spatial heterogeneity, and climate factor and vegetation type had strong explanatory power on the spatial distribution of NDVI, followed by soil type, while topographic factor had weak explanation. (3) In the vegetation zones, different soil zones, geomorphic zones and climate zones, the main environmental driving factors of NDVI spatial distribution were different. The average annual rainfall was the main environmental driving factors of NDVI spatial distribution with different explanatory power in aridisols zones, desert soil zones, entisols zones and each geomorphic zones. In the rest of zones, the main environmental driving factors of NDVI spatial distribution were soil type, vegetation type, sunshine duration or relative humidity. (4) The average annual rainfall had a strong explanatory power in the spatial distribution of NDVI and was the main environmental restricted factor for 85.20% of regional vegetation growth on the Loess Plateau, with 12.01% mainly influenced by soil factors, and the rest of region was affected by annual average temperature, sunshine duration or elevation. In conclusion, there was a strong spatial correlation between environmental factors and vegetation NDVI distribution on the Loess Plateau. However, due to the complexity of the geographical process of the Loess Plateau, the spatial correlation between environmental factors and vegetation NDVI had significant differences under different environmental conditions. Therefore, it is necessary to determine plant types in vegetation construction according to the environmental restricted factors of NDVI spatial distribution. It will improve the vegetation coverage and biodiversity on the premise of preventing soil desiccation and impoverishment, and promote the high-quality development of vegetation construction and ecological environmental protection on the Loess Plateau.