Using a new high-resolution air quality reanalysis dataset for China for five winters from December 2013 to February 2018, we examine the influence of large-scale circulation on daily PM2.5 variability through its direct effect on key regional meteorological variables over three major populated regions of China: Beijing–Tianjin–Hebei (BTH), the Yangtze River Delta (YRD) and the Pearl River Delta (PRD). In BTH, a shallow East Asian trough curbs northerly cold and dry air from the Siberian High, enhancing PM2.5 pollution levels. Weak southerly winds in eastern and southern China, associated with a weakened Siberian High, suppress horizontal dispersion, contributing to air pollution accumulation over YRD. In PRD, weak southerly winds and precipitation deficits over southern China are conducive to high PM2.5 pollution levels. To account for these dominant large-scale circulation–PM2.5 relationships, we propose three new circulation-based indices for predicting different levels of air pollution based on regional PM2.5 concentrations in each region: a 500 hPa geopotential height-based index for BTH, a sea level pressure-based index for YRD and an 850 hPa meridional wind-based index for PRD. These three indices can effectively distinguish clean days from heavily polluted days in these regions, assuming variation is solely due to meteorology. We also find that including the most important regional meteorological variable in each region improves the performance of the circulation-based indices in predicting daily PM2.5 concentrations on the regional scale. These results are beneficial to understanding and forecasting the occurrence of heavily polluted PM2.5 days in BTH, YRD and PRD from a large-scale perspective.