The WuShen counties in the hinterland of the Maowusu Sandland are located in the “ecological stress zone” of the forest–steppe desert, with low vegetation cover, a strong ecosystem sensitivity, and poor stability under the influence of human activities. Therefore, it is important to study and analyze the changes in vegetation growth in this region for the purpose of objectively evaluating the effectiveness of desertification control in China’s agricultural and pastoral intertwined zones, and formulating corresponding measures in a timely manner. In this paper, the spatial and temporal variations in the vegetation NDVI in the WuShen counties of the Maowusu Sandland and their response relationships with driving factors were investigated by using a trend test, center of gravity transfer model, partial correlation calculation, and residual analysis, and by using the MOD13A3 vegetation NDVI time series data from 2000 to 2020, as well as the precipitation, temperature, and potential evapotranspiration data from the same period. The results showed the following: ① The regional vegetation NDVI did not fluctuate significantly with latitude and longitude, and the NDVI varied between 0.227 and 0.375 over the 21-year period, with a mean increase of 0.13 for the region as a whole and an increase of 0.61 for the region of greatest change. Of the area, 86.83% experienced a highly significant increase, and the trend in increase around rivers and towns was higher than that in the northwestern inland flow area, with the overall performance of “low in the west and high in the east”. ② Only 2.07% of the vegetation NDVI center of gravity did not shift, and the response with climate factors was mainly characterized by having consistent or opposite center of gravity changes with precipitation and potential evapotranspiration. ③ Human activities have been the dominant factor in the vegetation NDVI change, with 75.89 percent of the area positively impacted by human activities, and human activities in the southwest inhibiting the improvement of vegetation in the area. The impact of human activities on the unchanged land type area is increasing, most obviously in the farmland area, and the impact of human activities on the changed land type area is gradually decreasing in the area where the farmland becomes impervious. The vegetation in the area above 1300 m above sea level is degraded by the environment and human activities. The research results can provide scientific support for the implementation of ecological fine management and the formulation of corresponding ecological restoration and desertification control measures in the Maowusu Sandland. At the same time, it is expected to serve as a baseline for other studies on the evolution of vegetation in agro-pastoral zones.