The Fen River Basin (FRB), an ecologically fragile region in China, exemplifies the intricate interplay between vegetation dynamics and both climatic and human-driven factors. This study leverages a 40-year (1982–2022) dataset, utilizing the kernel-based normalized difference vegetation index (kNDVI) alongside key climatic variables—rainfall (PRE), temperature (TMP), and solar radiation (SRAD)—to investigate vegetation variations and their drivers in the FRB, particularly in relation to the Grain for Green Program (GGP). Our analysis highlights significant greening across the FRB, with the kNDVI slope increasing by 0.0028 yr−1 and green-covered areas expanding by 92.8% over the study period. The GGP facilitated the greening process, resulting in a notable increase in the kNDVI slope from 0.0005 yr−1 to 0.0052 yr−1 and a marked expansion in the area of significant greening from 24.6% to 95.8%. Regional climate shifts, characterized by increased warming, heightened humidity, and a slight rise in SRAD, have further driven vegetation growth, contributing 75%, 58.7%, and 23.6% to vegetation dynamics, respectively. Notably, the GGP has amplified vegetation’s sensitivity to climatic variables, with areas significantly impacted by multiple climate factors expanding from 4.8% to 37.5%. Specially, PRE is the primary climatic influence, impacting 71.3% of the pertinent regions, followed by TMP (60.1%) and SRAD (30%). The integrated effects of climatic and anthropogenic factors, accounting for 47.8% and 52.2% of kNDVI variations, respectively, collectively influence 96% of the region’s vegetation dynamics. These findings underscore the critical role of climate change and human interventions in shaping vegetation patterns and provide a robust foundation for refining ecological conservation strategies, particularly in the context of global warming and land-use policies.