Studies have indicated that the adverse effects on human health and the decrease in visibility caused by fine particulate matter (PM2.5) exhibit spatial heterogeneity. Moreover, the environmental effects produced by different chemical compositions of PM2.5 vary on a regional scale. Therefore, understanding the spatiotemporal variations and chemical compositions of PM2.5 is necessary for assessing the regional impacts. Secondary inorganic PM2.5 (iPM2.5) is formed through chemical reactions between the base gas NH3 and acidic gas pollutants (e.g., NO2 or SO2). The major components of iPM2.5 include NH4+, SO42–, and NO3–. To fully comprehend the regional impacts of PM2.5, this research quantifies the spatiotemporal variations of iPM2.5 with the aim of evaluating the contributions from iPM2.5 to PM2.5 in North Carolina (NC). The concentrations (at 34 sites) and chemical components (at 7 sites) of PM2.5 from 2005 to 2014 were extracted from the EPA’s AirData, with the highest concentrations measured in the urban areas of central NC. Notably, PM2.5 concentrations have been significantly reduced over the past 10 years, with a concurrent decreasing trend in iPM2.5. Seasonal variation analysis indicates that PM2.5 concentrations were higher in summer and lower in winter; however, significant variation occurred only between 2005 and 2011. Although iPM2.5 formed the largest mass fraction of PM2.5 for 2005–2011, organic carbon matter (OCM) contributed the dominant share for 2012–2014. Significant seasonal variations in the iPM2.5 mass fractions were also observed, with NO3– and SO42– exhibiting inverse variations. This study links the ambient PM2.5 to various sources by revealing the spatiotemporal variations of PM2.5 and their associated chemical compositions in NC, thereby enabling the development of effective control and mitigation strategies.