In recent decades, environmental health risk caused by heavy metals in industrial wastewater (EHR-IHM) has become a serious issue globally, especially for China. Given the spatial difference of heavy metal emissions, hydrogeography, population distribution, etc., it is essential to estimate China’s EHR-IHM from a high-resolution perspective. Based on the framework of USEtox, this study constructs an environmental health risk assessment method for heavy metals discharged from industrial wastewater by coupling the Pollutant Accumulation Model (PAM). This method also considers the process of heavy metal flows between upstream and downstream areas. Based on this constructed method, we investigate the spatio-temporal distribution of EHR-IHM of As, Cd, Cr(VI), Hg, and Pb in China from 1999 to 2018. Results showed that the EHR-IHM in China increased rapidly during 1999–2007 and decreased gradually during 2007–2018, with the highest Damage Level (DL) of 6.8 × 104 disability-adjusted life years (DALY). As and Cr(VI) were the major heavy metal pollutants, which induced 58.9–70.6% and 23.9–36.2% of the total EHR-IHM, respectively. Intake of aquatic products was the dominant exposure route, accounting for over 84.1% of national EHR-IHM, followed by drinking water intake, accounting for 9.5–15.8%. Regarding spatial distribution, the regions with high EHR-IHM are mainly distributed in the middle–lower reaches of the Yangtze River, southeast coastal cities, Bohai Rim, etc.