The high-speed rail (HSR) network in China has experienced rapid development since the 2000s. In 2016, the State Council of the People's Republic of China issued a revised version of the “Mid- and Long-term Railway Network Plan”, detailing the expansion of the railway network and construction of an HSR system. In the future, the HSR construction efforts in China will further increase, which is considered to impact regional development and air pollutant emissions. Therefore, in this paper, we apply a transportation network-multiregional computable general equilibrium (CGE) model to estimate the dynamic effects of HSR projects on economic growth, regional disparities, and air pollutant emissions in China. The results indicate that HSR system improvement could generate a positive economic impact but could also increase emissions. The gross domestic product (GDP) growth per unit investment cost stimulated by HSR investment is found to be the largest in eastern China but the smallest in the northwest regions. Conversely, HSR investment in Northwest China contributes to a substantial reduction in regional disparities in terms of the GDP per capita. In regard to air pollution emissions, HSR construction in South-Central China results in the largest increase in CO2 and NOX emissions, while for CO, SO2, and fine particulate matter (PM2.5) emissions, the largest increase occurs due to HSR construction in Northwest China. At the regional level, the provinces with large changes in accessibility also experience large changes in their air pollutant emissions.