In this study we investigated the effectiveness of air purifiers and in-line filters in ventilation systems working simultaneously inside various classrooms at the University of Southern California (USC) main campus. We conducted real-time measurements of particle mass (PM), particle number (PN), and carbon dioxide (CO₂) concentrations in nine classrooms from September 2021 to January 2022. The measurement campaign was carried out with different configurations of the purifier (i.e., different flow rates) while the ventilation system was continuously working. Our results showed that the ventilation systems in the classrooms were adequate in providing sufficient outdoor air to dilute indoor CO₂ concentrations due to the high air exchange rates (2.63–8.63 h⁻¹). The particle penetration coefficients (P) of the investigated classrooms were very low for PM (<0.2) and PN (<0.1), with the exception of one classroom, corroborating the effectiveness of in-line filters in the ventilation systems. Additionally, the results showed that the efficiency of the air purifier exceeded 95% in capturing ultrafine and coarse particles and ranged between 82–88% for particles in the accumulation range (0.3–2 µm). The findings of this study underline the effectiveness of air purifiers and ventilation systems equipped with efficient in-line filters in substantially reducing indoor air pollution.