SO3 exists in the atmosphere in the form of sulfuric acid aerosol, seriously polluting the environment and damaging the safety of boiler equipment. This study focuses on the homogeneous formation mechanism of SO3 in post-flame region. Experiments and simulations investigated the influences of combustion parameters on SO3 generation. Formation of SO3 was considered to be affected by factors such as temperature and the concentration of O2, SO2, NO, and H2O. With raising the temperature, SO3 concentration initially increased but then decreased. The concentration of SO3 reaches the maximum at about 1000°C. SO2 can promote the formation of SO3 over a certain temperature range. An increase in O2 concentration promoted the formation of O and OH radicals, which enhanced generation of SO3 from SO2. The presence of NO resulted in direct and indirect interactions between NOx and SOx species for different reaction sets, potentially enhancing SO3 generation. With an increase in H2O concentration, SO3 formation increased rapidly initially, before plateauing. ROP (rate of production) analyses and sensitivity analyses suggested that adding H2O will produce O and OH, which have a strong influence on SO3 formation. Furthermore, sensitivity analysis indicated that radicals play an important role in SO3 formation, and the direct reaction between SO2 and NO2 is also significant to SO3 formation.