Vegetation status reflects the quality of regional environment, and vegetation assessment plays a crucial role in the assessment of ecological changes. As the main component of nature reserves (NRs), vegetation provides an important habitat for wild plants and animal; thus, the vegetation status in NRs is closely related to the survival conditions of the wildlife. Furthermore, vegetation changes can reflect the interaction between natural and anthropogenic activities. Accordingly, analysis of vegetation changes and their magnitude can help to assess the efficacy of conservation in a nature reserve. At the same time, examining the vegetation changes and exploring their driving factors are of great importance for the conservation and management of NRs. Changbai Mountain National Nature Reserve (CMNR) is one of the earliest nature reserves established in China. Its biodiversity is high with 9 species of amphibians, 12 species of reptiles, 24 species of fish, 56 species of mammals, 230 species of birds, and 1255 species of insects. It is also home to 430 species of fungi, 200 species of lichens, 311 species of mosses and liverworts, 78 species of ferns, 11 species of gymnosperms, and 1325 species of angiosperms. This paper aimed to identify the extent of changes in vegetation cover between 2000 and 2010 in order to better protect the vegetation in CMNR. Based on the normalized difference vegetation index data provided by the Moderate Resolution Imaging Spectroradiometer, we examined the temporal and spatial variation of vegetation and its driver during the last 10 years, using methods of monadic linear regression trend analysis and correlation coefficient test. Results showed that in CMNR most of the vegetation, accounting for 88.95%, was stable in the past 10 years, 9.71% of the total area of vegetation improved significantly, and only 1.34% of vegetation degraded significantly, suggesting that the vegetation conservation in the reserve was successful overall. When considering the driving factors of vegetation variation, the proportion of vegetation that changed was significantly correlated with the temperature and it was slightly larger than the proportion of vegetation significantly affected by the precipitation, indicating that temperature have a slightly greater effect on vegetation than precipitation. Both factors were negatively correlated with vegetation changes, but the area with significant correlation for both factors was less than 8%. In general, the influence of temperature and precipitation on vegetation was limited. The change in vegetation cover in CMNR was different on different terrains, i.e., vegetation degradation was enhanced with the increase of altitude and slope. Especially, Betula ermanii forest and tundra distributed in the area more than 1800 m above sea level and within the scope of slope from 26 to 35° were degraded significantly. Beside the topography factors, growing tourism and unregulated development and construction have also affected the degradation of the part of vegetation in CMNR. Although only 1.34% of vegetation is degraded significantly in CMNR, great attention should be given by relevant administrative departments. Therefore, in order to protect the existing vegetation more effectively and restore the degraded vegetation, as well as provide references for scientific management of CMNR, we have provided three suggestions:(1) to build tundra protection facilities in touristic regions within the tundra in order to strictly limit the expansion of touristic activities; (2) to speed up restoration of the degraded Betula ermanii forest and tundra with artificial stimulation measures; and (3) to block or change the course of No. 302 provincial road crossing the nature reserve in southern slope.