As global climate change intensifies and human activities escalate, changes in vegetation cover, an important ecological indicator, hold significant implications for ecosystem protection and management. Shandong Province, a critical agricultural and economic zone in China, experiences vegetation changes that crucially affect regional climate regulation and biodiversity conservation. This study employed normalized difference vegetation index (NDVI) data, combined with climatic, topographic, and anthropogenic activity data, utilizing trend analysis methods, partial correlation analysis, and Geodetector to comprehensively analyze the spatiotemporal variations and primary driving factors of vegetation cover in Shandong Province from 2001 to 2020. The findings indicate an overall upward trend in vegetation cover, particularly in areas with concentrated human activities. Climatic factors, such as precipitation and temperature, exhibit a positive correlation with vegetation growth, while land use changes emerge as one of the key drivers influencing vegetation dynamics. Additionally, topography also impacts the spatial distribution of vegetation to a certain extent. This research provides a scientific basis for ecological protection and land management in Shandong Province and similar regions, supporting the formulation of effective vegetation restoration and ecological conservation strategies.