China’s economy is transitioning from high-speed to high-quality development, making coordination between economic factors increasingly important. Human capital (HC) and infrastructure (INFRA) are important elements of economic development, and the coupling coordination of the two can have a non-negligible impact on regional economies’ high-quality development. Therefore, this study measures the coupling coordination degree (CCD) of HC and INFRA based on data of 184 prefecture-level cities in China from 2011 to 2019, and comprehensively examines the impact effect and mechanism of the CCD on high-quality economic development (HQED). The relevant results are threefold. (1) Compared with single factors, the degree of HC-INFRA CCD can promote HQED more efficiently. (2) A significant single-threshold effect is evident in the promotion of HQED by the degree of HC-INFRA CCD, and a smaller city size and more extensive higher education institutions promote a stronger threshold effect. (3) Factor allocation and factor efficiency are significant transmission mechanisms of the HC-INFRA CCD affecting HQED, and the mediating effect of the capital-labor force allocation path accounts for 66.28% of the total indirect effect. The results provide empirical evidence verifying that HC-INFRA CCD promotes HQED, along with insightful reference suggestions for formulating relevant macro policies and promoting high-quality urban economic development.