As global climate change intensifies, arid land ecosystems face increasing challenges. Vegetation, a key indicator of climate variation, is highly responsive to meteorological factors such as temperature (Tem), precipitation (Pre), and soil moisture (SM). Understanding how fractional vegetation cover (FVC) responds to climate change in arid regions is critical for mitigating its impacts. This study utilizes MOD13Q1-NDVI data from 2000 to 2022, alongside corresponding Tem, Pre, and SM data, to explore the dynamics and underlying mechanisms of SM and FVC in the context of climate change. The results reveal that both climate change and human activities exacerbate vegetation degradation, underscoring its vulnerability. A strong correlation between FVC and both Tem and Pre suggests that these factors significantly influence FVC variability. In conclusion, FVC in the lower reaches of the Heihe River is shaped by a complex interplay of Tem, Pre, SM, and human activities. The findings provide a scientific basis and decision-making support for ecological conservation and water resource management in the lower reaches of the Heihe River, aiding in the development of more effective strategies to address future climate challenges.