Abstract: The Shennongjia National Nature Reserve serves as a critical ecological barrier in central China and a global biodiversity hotspot, playing a key role in maintaining regional ecological security. However, under the dual pressures of global climate change and increasing human activities, the long-term dynamics of vegetation within the reserve and their underlying driving mechanisms have not yet been fully explained. To address this research gap, this study systematically analyzed the spatiotemporal patterns of vegetation evolution in the Shennongjia region from 2000 to 2023 through multi-source remote sensing data (MODIS EVI) and meteorological datasets (temperature, precipitation, and solar radiation). The study integrated Theil-Sen median trend analysis, Mann-Kendall test, and multiple residual trend analysis to quantitatively separate the relative contributions of climatic factors and human activities to vegetation changes across different functional zones. The results show that from 2000 to 2023, vegetation conditions in the Shennongjia Nature Reserve exhibited a significantly positive development trend. The Enhanced Vegetation Index (EVI) displayed an overall fluctuating upward pattern, with two rapid growth phases occurring between 2000—2005 and 2018—2022, while remaining relatively stable during other periods. This confirms the overall effectiveness of ecological restoration measures such as the Natural Forest Protection Project. Spatially, vegetation dynamics showed notable heterogeneity. Vegetation coverage in the core zone remained consistently high and stable, reflecting the outcomes of strict conservation measures. In contrast, vegetation changes in the experimental zone and buffer zone were more complex and variable due to human disturbance, while the overall trend remained positive. The core conclusion of this study is that the driving factors of vegetation change in Shennongjia exhibit spatial variation. Vegetation dynamics in the reserve are jointly driven by climate change and human activities, with human activities contributing at a higher average rate than climatic factors. The spatial patterns of driving factors differ significantly. Vegetation changes in the southwestern region and the core zone are primarily climate-driven, where vegetation shows high sensitivity to fluctuations in natural meteorological factors. In the northeastern region and areas surrounding the reserve (mainly the experimental zone), human activities play a dominant role. Positive anthropogenic interventions, such as ecological engineering and conservation policies, have been decisive in reversing vegetation degradation and promoting restoration. Although the overall ecological quality of the Shennongjia National Nature Reserve has improved, the experimental zone is still affected by localized human disturbances from tourism development and infrastructure construction. This study recommends that future management strategies adopt differentiated approaches. The core zone should focus on strengthening climate change monitoring and enforcing strict conservation measures. The experimental zone needs to balance ecological carrying capacity with sustainable development. The findings provide scientific support for the refined management of forest ecosystems and the optimization of functional zoning in nature reserves.