High concentrations of PM2.5 are universally considered as a main cause for haze formation. Therefore, it is important to identify the spatial heterogeneity and influencing factors of PM2.5 concentrations for regional air quality control and management. In this study, PM2.5 data from 2000 to 2015 was determined from an inversion of NASA atmospheric remote sensing images. Using geo-statistics, geographic detectors, and geo-spatial analysis methods, the spatio-temporal evolution patterns and driving factors of PM2.5 concentration in China were evaluated. The main results are as follows. (1) In general, the average concentration of PM2.5 in China increased quickly and reached its peak value in 2006; subsequently, concentrations remained between 21.84 and 35.08 μg/m3. (2) PM2.5 is strikingly heterogeneous in China, with higher concentrations in the north and east than in the south and west. In particular, areas with relatively high PM2.5 concentrations are primarily in four regions, the Huang-Huai-Hai Plain, Lower Yangtze River Delta Plain, Sichuan Basin, and Taklimakan Desert. Among them, Beijing-Tianjin-Hebei Region has the highest concentration of PM2.5. (3) The center of gravity of PM2.5 has generally moved northeastward, which indicates an increasingly serious haze in eastern China. High-value PM2.5 concentrations have moved eastward, while low-value PM2.5 has moved westward. (4) Spatial autocorrelation analysis indicates a significantly positive spatial correlation. The “High-High” PM2.5 agglomeration areas are distributed in the Huang-Huai-Hai Plain, Fenhe-Weihe River Basin, Sichuan Basin, and Jianghan Plain regions. The “Low-Low” PM2.5 agglomeration areas include Inner Mongolia and Heilongjiang, north of the Great Wall, Qinghai-Tibet Plateau, and Taiwan, Hainan, and Fujian and other southeast coastal cities and islands. (5) Geographic detection analysis indicates that both natural and anthropogenic factors account for spatial variations in PM2.5 concentration. Geographical location, population density, automobile quantity, industrial discharge, and straw burning are the main driving forces of PM2.5 concentration in China.