Vegetation is an important part of the ecological environment, and the Heihe River Basin (HHRB) is typical of the inland river basin of Northwest China. Analyzing the changes in the ecological environment and its driving factors in the HHR plays a crucial role in the Northwest Arid Region of China (NWARC). In this paper, we analyzed the spatiotemporal characteristics of NDVI in the HHR and quantified the influence of the driving factors of NDVI using a GeoDetector. It analyzed the correlation of the main driving factors and discussed the future trend of NDVI. Our research indicates the change of NDVI from 2000 to 2022 in the HHR; it has a significant upward trend, and there is significant spatial differentiation. It shows a pattern that increases from northwest to southeast. The area of improved vegetation in the basin accounted for 77.46%, and the degraded area was only 9.71%, which resulted in significant results of ecological restoration. In addition, the main influence detection results of each environmental factor of NDVI in the catchment are elevation, sunshine duration, precipitation, and temperature. The explanatory power of any two-factor interaction on the spatial variations of NDVI in the basin was enhanced compared with that of the single-factor explanation. Finally, the maximum and suitable ranges of risk of the environmental factors influencing NDVI were obtained. 61.92% of the vegetation in the basin will continue to be improved in the future. This study can provide a theoretical basis for ecological environmental protection and regional sustainable development in NWARC.