Numerous studies have confirmed that climate change leads to a decrease in the net ecosystem productivity (NEP) of terrestrial ecosystems and alters regional carbon source/sink patterns. However, the response mechanism of NEP to climate change in the arid regions of Central Asia remains unclear. Therefore, this study combined the Carnegie–Ames–Stanford approach (CASA) and empirical models to estimate the NEP in Central Asia and quantitatively evaluate the sensitivity of the NEP to climate factors. The results show that although the net primary productivity (NPP) in Central Asia exhibits an increasing trend, it is not significant. Soil heterotrophic respiration (RH) has increased significantly, while the NEP has decreased at a rate of 6.1 g C·m⁻²·10 a⁻¹. Spatially, the regional distribution of the significant increase in RH is consistent with that of the significant decrease in the NEP, which is concentrated in western and southern Central Asia. Specifically, the NPP is more sensitive to precipitation than temperature, whereas RH and NEP are more sensitive to temperature than precipitation. The annual contribution rates of temperature and precipitation to the NEP are 28.79% and 23.23%, respectively. Additionally, drought has an important impact on the carbon source/sink in Central Asia. Drought intensified from 2001 to 2008, leading to a significant expansion of the carbon source area in Central Asia. Therefore, since the start of the 21st century, climate change has damaged the NEP of the Central Asian ecosystem. Varying degrees of warming under different climate scenarios will further aggravate the expansion of carbon source areas in Central Asia. An improved understanding of climate change impacts in Central Asia is critically required for sustainable development of the regional economy and protection of its natural environment. Our results provide a scientific reference for the construction of the Silk Road Economic Belt and global emissions reduction.