The One Health concept acknowledges the importance of multiple dimensions in controlling antimicrobial resistance (AMR). However, our understanding of how anthropological, socioeconomic, and environmental factors drive AMR at a national level remains limited. To explore associations between potential contributing factors and AMR, this study analyzed an extensive database comprising 13 major antibiotic-resistant bacteria and over 30 predictors (e.g., air pollution, antibiotic usage, economy, husbandry, public services, health services, education, diet, climate, and population) from 2014 to 2020 across China. The multivariate analysis results indicate that fine particulate matter with a diameter of 2.5 μm or less (PM_2.5) is associated with AMR, accounting for 12% of the variation, followed by residents’ income (10.3%) and antibiotic usage density (5.1%). A reduction in PM_2.5 of 1 µg·m⁻³ is linked to a 0.17% decrease in aggregate antibiotic resistance (p < 0.001, R² = 0.74). Under different scenarios of China’s PM_2.5 air-quality projections, we further estimated the premature death toll and economic burden derived from PM_2.5-related antibiotic resistance in China until 2060. PM_2.5-derived AMR is estimated to cause approximately 27 000 (95% confidence interval (CI): 646848 830) premature deaths and about 0.51 (95% CI; 0.12–0.92) million years of life lost annually in China, equivalent to an annual welfare loss of 8.4 (95%CI; 2.0–15.0) billion USD. Implementing the “Ambitious Pollution 1.5 °C Goals” scenario to reduce PM_2.5 concentrations could prevent roughly 14 000 (95% CI; 3324–26 320) premature deaths—with a potential monetary value of 9.8 (95% CI; 2.2–17.6) billion USD—from AMR by 2060. These results suggest that reducing air pollution may offer co-benefits in the health and economic sectors by mitigating AMR.