Secondary inorganic fine particulate matter (iPM2.5) constitutes a significant amount of atmospheric PM2.5. The formation of secondary iPM2.5 is characterized by thermodynamic equilibrium gas-particle partitioning of gaseous ammonia (NH3) and aerosol ammonium (NH4+). To develop effective control strategies of atmospheric PM2.5, it is essential to understand the responses of secondary iPM2.5 to different precursor gases. In southeastern North Carolina, the NH3 is excessive to fully neutralize acid gases (NH3-rich condition). The NH3-rich condition is mainly attributed to the significant NH3 emissions in the region, especially the large amounts of animal feeding operation (AFO) facilities. To gain some insights into the impact of NH3 on the formation of secondary iPM2.5 in this region, responses of iPM2.5 to precursor gases under different ambient conditions were investigated based upon three-year monitoring data of iPM2.5 chemical compositions, gaseous pollutants, and meteorological conditions. The gas ratio (GR) was used to assess the neutralization degree of NH3, and ISORROPIA II model simulation was used to examine the responses of iPM2.5 to the changes in total NH3, total sulfuric acid (H2SO4) and total nitric acid (HNO3). It was discovered that under different ambient temperature and humidity conditions, the responses of iPM2.5 to precursor gases are different. In general, the iPM2.5 responds to total NH3 nonlinearly, whereas the responses of iPM2.5 to total H2SO4 and total HNO3 are linear. In NH3-rich regions, iPM2.5 is not sensitive to the change of total NH3, but it is very sensitive to the changes of total H2SO4 and/or total HNO3. Reduction of total H2SO4 leads to significant reduction of iPM2.5; thus, it is more effective than reducing total HNO3 and total NH3 to reduce iPM2.5 concentration. The research provides insight into PM2.5 control and regulation in NH3-rich regions.