Vegetation, being a core component of ecosystems, is known to be influenced by natural and anthropogenic factors. Studying vegetation cover dynamics variation and its drivers is critical to understanding the interactions between vegetation and ecosystems. The Loess Plateau (LP) is located in a semi-arid and semi-humid region with severe soil erosion and fragile ecology. This paper used the annual maximum Normalized Difference Vegetation Index (NDVIymax) and growing season mean NDVI (NDVIgsmean) as the vegetation cover indicator. The vegetation cover variation of LP from 2000 to 2020 was analyzed using Sen's slope and Mann-Kendall test. Then the in-fluence of natural and anthropogenic factors on the driving mechanisms of spatial vegetation differentiation was explored by the Geodetector model. The results revealed that the growth trends of NDVIymax and NDVIgsmean were 0.075/10 years and 0.038/10 years, respectively, and the areas with improved vegetation cover accounted for 92.67 % and 88.58 % of the total area. The vegetation cover of the southeastern and northern parts of the LP decreased significantly; however, the central, southwestern, and northeastern parts exhibited a remarkable improvement. Precipitation, vegetation type, soil type, temperature, and land use type were the key driving forces, ranked differently on NDVIymax and NDVIgsmean. However, precipitation was the most critical factor both on NDVI(ymax )and NDVIgsmean. The interaction detection showed non-linear and mutual enhancement, with no independent factor. The findings of our study can assist in identifying the vegetation cover status of the LP, as well as the driving forces, which can provide theoretical support for the formulation of environmental conservation policies.