The major industrial cities of Bangladesh are experiencing significant air-pollution-related problems due to the increased trend of particulate matter (PM2.5) and other pollutants. This paper aimed to investigate and understand the relationship between PM2.5 and land use and climatic variables to identify the riskiest areas and population groups using a geographic information system and regression analysis. The results show that about 41% of PM2.5 concentration (μg/m3) increased within 19 years (2002–2021) in the study area, while the highest concentration of PM2.5 was found from 2012 to 2021. The concentrations of PM2.5 were higher over barren lands, forests, croplands, and urban areas. From 2002–2021, the concentration increased by about 64%, 62.7%, 57%, and 55% (μg/m3) annually over barren lands, forests, cropland, and urban regions. The highest concentration level of PM2.5 (84 μg/m3) among other land use classes was found in urban areas in 2021. The regression analysis shows that air pressure (hPa) (r2 = −0.26), evaporation (kg m−2) (r2 = −0.01), humidity (kg m−2) (r2 = −0.22), rainfall (mm/h) (r2 = −0.20), and water vapor (kg m−2) (r2 = −0.03) were negatively correlated with PM2.5. On the other hand, air temperature (k) (r2 = 0.24), ground heat (W m−2) (r2 = 0.60), and wind speed (m s−1) (r2 = 0.34) were positively correlated with PM2.5. More than 60 Upazilas were included in the most polluted areas, with a total population of 11,260,162 in the high-risk/hotspot zone (1,948,029 aged 0–5, 485,407 aged 50–69). Governmental departments along with policymakers, stainable development practitioners, academicians, and others may use the main results of the paper for integrated air pollution mitigation and management in Bangladesh as well as in other geographical settings worldwide.