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Evaluating the responses of net primary productivity (NPP) to climate change is essential for regional ecosystem management and adaptations to climate change. The Yangtze River Economic Belt (YREB) is a key ecological functional area and hotspot of carbon sequestration in China due to the high degree of forest coverage. We used a process-based ecosystem model to project terrestrial NPP and analyzed the response to climate change over the 21st century in the YREB under two representative concentration pathway (RCP) scenarios using the regional climate model. The results show that the projection of NPP generally increased by 13.5% under RCP4.5 and 16.4% under RCP8.5 in the middle of the century, by 23% under RCP4.5, and by 35% under RCP8.5 in the late term of the century compared with that from a reference period of current climate conditions (1985–2006). The rate of NPP change under the RCP8.5 scenario is higher than that under the RCP4.5 scenario. Similarly, the NPP is also projected to increase both with 1.5 and 2 °C global warming targets in the YREB. The magnitudes of NPP increment are approximately 14.7% with 1.5 °C and 21% with 2 °C warming targets compared with the current climate, which are higher than the average increments of China. Although NPP is projected to increase under the two scenarios, the tendency of NPP increasingly exhibits a slowdown after the 2060 s under the RCP4.5 scenario, and the growth rate of NPP is projected to drop in more than 31% of regional areas with the additional 0.5 °C warming. In contrast, under the RCP8.5 scenario, the trend in NPP keeps rising substantially, even above 2 °C global warming. However, the NPP in some provinces, including Jiangxi and Hunan, is projected to reduce at the end of the 21st century, probably because of temperature rises, precipitation decreases, and water demand increases. Generally, the NPP is projected to increase due to climate change, particularly temperature increase. However, temperature rising does not always show a positive effect on NPP increasing; the growth rate of NPP will slow down under the RCP4.5 scenario in the mid-late 21st century, and NPP will also reduce by the end of this century under the RCP8.5 scenario in some places, probably presenting some risks to terrestrial ecosystems in these areas, in terms of reduced functions and service decline, a weakened capacity of carbon sequestration, and reduced agricultural production. [ABSTRACT FROM AUTHOR]