Fine particulate matter (PM_2.5) is an airborne pollutant associated with negative acute and chronic human health outcomes. Although the majority of PM_2.5 research has focused on outdoor exposures, people spend the majority of their time indoors, where PM_2.5 of outdoor origin can penetrate. In this work, we measured indoor PM_2.5 continuously for one year in 37 urban commercial offices with mechanical or mixed-mode ventilation in China, India, the United Kingdom, and the United States. We found that indoor PM_2.5 concentrations were generally higher when and where outdoor PM_2.5 was elevated. In India and China, mean workday indoor PM_2.5 levels exceeded the World Health Organization's 24-hour exposure guideline of 25 $\mu$g/m³ about 17% and 27% of the time, respectively. Our statistical models found evidence that the operation of mechanical ventilation systems could mitigate the intrusion of outdoor PM_2.5: during standard work hours, a 10 $\mu$g/m³ increase in outdoor PM_2.5 was associated with 19.9% increase in the expected concentration of indoor PM_2.5 (p < 0.0001), compared to a larger 23.4% increase during non-work hours (p < 0.0001). Finally, our models found that using filters with ratings of MERV 13–14 or MERV 15+ was associated with a 30.9% (95% CI: −55.0%, +6.2%) or 39.4% (95% CI: −62.0%, −3.4%) reduction of indoor PM_2.5, respectively, compared to filters with lower MERV 7–12 ratings. Our results demonstrate the potential efficacy of mechanical ventilation with efficient filtration as a public health strategy to protect workers from PM_2.5 exposure, particularly where outdoor levels of PM_2.5 are elevated.