The oxidative potential (OP) of fine particulate matter (PM2.5) is a more robust health impact indicator than mass concentration alone. While China's stringent air pollution controls have significantly reduced PM2.5 levels, the temporal evolution of OP and its relationship with PM2.5 remain unclear. This study establishes a national PM2.5 OP database (2000–2020) using a source-oriented CMAQ model. Key findings reveal that OP decreases alongside PM2.5 concentrations over the study period, but the decline in OP (16%) is less pronounced than that of PM2.5 (37%) after 2012, leading to a 35% increase in mass-normalized OP (OPm). Source apportionment analysis identifies distinct phase-specific drivers: anthropogenic secondary organic aerosols (ASOA) were the dominant contributor to OP increases (∼68%) prior to 2012, while reductions in transportation, power generation, and biomass burning emissions drove OP declines during 2012–2017. Post-2017, stringent controls on anthropogenic non-methane volatile organic compounds (NMVOCs) made ASOA the dominant declining source. Notably, urban-rural disparities in OP exposure exceed those of PM2.5 mass concentrations, primarily reflecting differences in dominant emission sources. As the first nationwide study to systematically evaluate the decoupling of PM2.5 mass and OP trends in China, these findings underscore the need for targeted strategies to mitigate PM-related health risks.