Air quality is often assessed using particulate matter (PM) mass concentration without considering its toxicity, thus possibly leading to improper control policies or inadequate health protection. Here, we studied differences in oxidative potentials (OPs) of PM samples collected using automobile air conditioning (AC) filters from 19 global cities, including influences from microbial contents. Dithiothreitol (DTT) assay showed remarkable differences in the PM OPs among cities (p-values ≤ 0.001, Kruskal-Wallis test). For example, the normalized index of oxidant generation (NIOG) of PM samples in San Francisco (2.20 × 10^(−2), annual average PM_(10) = 16 μg/m^3) was found to be twice that in Beijing (1.14 × 10^(−2), annual average PM_(10) = 135 μg/m^3). Limulus amebocyte lysate (LAL) assay found that PM-borne endotoxin ranged from 12.16 EU/mg (Florianopolis, Brazil) to 2518.23 EU/mg (Chennai, India) among cities. Besides, culturing method and real-time qPCR revealed significant differences up to ∼100-fold in both bacterial and fungal levels among 19 cities. Spearman's correlation analysis implied that PM-borne microbes such as bacteria and fungi as well as metals could strongly influence the PM OP. As an example, our results in Xi'an, China further suggest that the PM_(2.5) OP evolves for a particular city over the time, which is attributable to both the urbanization and air pollution control measures. This work highlights the importance in optimizing the current air quality control measures by considering the toxicity factor and its microbial constituents.