The vegetation ecosystem in the southern hilly region of China (SHRC) plays a crucial role in the country’s carbon reservoir. Clarifying the dynamics of net primary productivity (NPP) in this area and its response to climate factors in the context of climate change is important for national forest ecology, management, and carbon neutrality efforts. This study, based on remote sensing and meteorological data spanning the period 2001 to 2021, aims to unveil the spatiotemporal patterns of vegetation productivity and climate factors in the southern hilly region, explore interannual variation characteristics of vegetation productivity with altitude, and investigate the response characteristics of NPP to various climate factors. The results indicate that from 2001 to 2021, the annual average NPP in the southern hilly region had a significant increasing trend of 2.13 ± 0.78 g m−2 a−1. The trend of NPP varies significantly with altitude. Despite a general substantial upward trend in vegetation NPP, regions at lower elevations exhibit a faster rate of increase, suggesting a diminishing difference in the NPP of different elevation ranges. The overall rise in average temperature has positive implications for the southern hilly region, while the impact of precipitation on vegetation NPP demonstrates noticeable spatial heterogeneity. Regions in which vegetation NPP is significantly negatively correlated with precipitation are mainly concentrated in the southern areas of Guangdong, Fujian, and Jiangxi provinces. In contrast, other regions further away from the southeastern coast tend to exhibit a positive correlation. Over the past two decades, there has been an asymmetry in the diurnal temperature variation in the SHRC, with the nighttime warming rate being 1.8 times that of the daytime warming rate. The positive impact of daytime warming on NPP of vegetation is more pronounced than the impact of nighttime temperature changes. Understanding the spatiotemporal patterns of NPP in the SHRC and the characteristics of its response to climate factors contributes to enhancing our ability to protect and manage vegetation resources amidst the challenges of global climate change.