The Source Region of the Yellow River is situated in the hinterland of Qing-Tibetan Plateau, with very fragile ecosystem. The Source Region of the Yellow River is facing problems such as biodiversity and ecosystem degradation. Ecological protection and high-quality development of the Source Region of the Yellow River has been risen to be one of the key concerns of the national strategy. Land use and vegetation cover are important factors affecting habitat quality. More and more attention has been paid to quantitative evaluation of the impact of the change of land use types, intensity and patterns to habitat quality and the change of the spatiotemporal pattern of vegetation cover to habitat quality. However, the coupling effects of land use and vegetation cover on the habitat quality of the Source Region of the Yellow River are still unclear. Based on the data of land use and the normalized difference vegetation index (NDVI) of vegetation growing season in the Source Region of the Yellow River in 2000 and 2015, this study used the InVEST model to explore the temporal and spatial changes of the habitat quality in the source area of the Yellow River in different periods, and used the geographical weighted regression (GWR) model to quantitatively analyze the coupling effect of land use and NDVI on the evolution of habitat quality. The results showed that land-use types had mainly changed from unused land to grassland in 2000 and 2015 in the Source Region of the Yellow. Overall NDVI in the Source Region of the Yellow River increased during the growing season in 2000 and 2015. From the perspective of spatial distribution, the habitat quality generally presented a spatial pattern of low in the north and high in the south. The high values were distributed in the southern and central regions, and the low values were distributed in the Buqing Mountain in the north, the high-altitude areas in the northeast and along the Yellow River in Yellow River Township. Compared with 2000, the habitat quality in the Source Region of the Yellow River in 2015 increased by 11.47% on average. Both the grassland and NDVI had a significantly positive correlation with the habitat quality, and NDVI dominated the change of habitat quality. The results of this study highlight the leading role of NDVI in improving the habitat quality in the Source Region of the Yellow River and can provide a reference for future ecological protection of the source region.