Secondary inorganic fine particulate matter (iPM2.5) constitutes a significant amount of the 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 strategies for controlling atmospheric PM2.5, it is essential to understand the responses of secondary iPM2.5 to different precursor gases. In southeastern North Carolina, the amount of NH3 is in excess to fully neutralize acidic gases (i.e., NH3-rich conditions). NH3-rich conditions are mainly attributed to the significant NH3 emissions in the region, especially from the large amounts of animal feeding operation (AFO). To gain a better understanding of the impact of NH3 on the formation of secondary iPM2.5 in this area, the responses of iPM2.5 to precursor gases under different ambient conditions were investigated based upon three-year monitoring data of the chemical components in iPM2.5, gaseous pollutants, and meteorological conditions. The gas ratio (GR) was used to assess the degree of neutralization via NH3, and ISORROPIA II model simulation was used to examine the responses of iPM2.5 to changes in the total NH3, the total sulfuric acid (H2SO4), and the total nitric acid (HNO3). It was discovered that under different ambient temperature and humidity conditions, the responses of iPM2.5 to precursor gases vary. In general, iPM2.5 responds nonlinearly to the total NH3 but linearly to the total H2SO4 and the total HNO3. In NH3-rich regions, iPM2.5 is not sensitive to changes in the total NH3, but it is very sensitive to changes in the total H2SO4 and/or the total HNO3. Reducing the total H2SO4, as opposed to the total HNO3 or the total NH3, leads to a significant reduction in iPM2.5 and is thus a more effective strategy for decreasing the concentration of iPM2.5. This research provides insight into controlling and regulating PM2.5 in NH3-rich regions.