Fine particulate matter smaller than 2.5 μm (PM_2.5) in size can significantly affect human health, atmospheric visibility, climate, and ecosystems. PM_2.5 has become the major air pollutant in most cities of China. However, influencing factors and their interactive effects on PM_2.5 concentrations remain unclear. This study used a geographic detector method to quantify the effects of anthropogenic precursors (AP) and meteorological factors on PM_2.5 concentrations in cities of China. Results showed that impacts of meteorological conditions and AP on PM_2.5 have significant spatio-temporal disparities. Temperature was the main influencing factor throughout the whole year, which can explain 27% of PM_2.5 concentrations. Precipitation and temperature were primary impacting factors in southern and northern China, respectively, at the annual time scale. In winter, AP had stronger impacts on PM_2.5 in northern China than in other seasons. Ammonia had stronger impacts on PM_2.5 than other anthropogenic precursors in winter. The interaction between all factors enhanced the formation of PM_2.5 concentrations. The interaction between ammonia and temperature had strongest impacts at the national scale, explaining 46% (q = 0.46) of PM_2.5 concentrations. The findings comprehensively elucidated the relative importance of driving factors in PM_2.5 formation, which can provide basic foundations for understanding the meteorological and anthropogenic influences on the concentration patterns of PM_2.5.