Computational modeling of the combustion systems not only depends on the flow field typology but also requires well considering the turbulence-reaction interactions. Complex combustion chambers can increase numerical costs dramatically. This paper addresses a novel CFD-based chemical reactor network (CFD-CRN) integrated approach to predict combustion byproducts with high accuracy. This methodology uses turbulence intensity as a determining factor to generate clusters of reactors. The CFD simulations were performed with fine grids using the GRI-Mech 2.11 methane-air combustion mechanism with 277 elementary reactions of 49 species. The GRI-Mech 3.0 including NO formation and reburn chemistry, with 53 species and 325 reactions, is used for the CRN analysis. Implementing the CFD-based CRN, the authors found that the rate of production of NOx from the prompt, thermal, and N2O pathways are calculated as 47.37%, 22.18%, 30.45%, and 40.24%, 29.13%, and 30.63% for the Sandia flames D and E, respectively. The computational fluid dynamics reports for those pathways are predicted as 50.39%, 19.78%, 29.83%, and about 43.58%, 28.45%, and 27.97% entire the Sandia flames D and E, in order. It is deduced that the application of the hybrid CFD-CRN in combustion systems is not only reliable for its high accuracy but also is noticeably efficient for fewer CPU requirements and numerical costs, especially in industrial combustion systems.