This study addresses the unclear mechanism of multi-parameter coupling effects in low-nitrogen combustion operations of industrial boilers. This study investigates a 2.8 MW natural gas boiler. Orthogonal experimental design and numerical simulation are employed. The main effects and interactions of the excess air coefficient, thermal load, and flue gas recirculation (FGR) rate on combustion characteristics and NOx emissions are systematically analyzed. The results show that the FGR rate is the most critical factor affecting NOx emissions; increasing it significantly reduces the combustion temperature and oxygen concentration, lowering NOx emissions to below 30 mg/Nm3. Significant interactions exist among the parameters, and the synergistic regulation of the excess air coefficient and FGR rate has a decisive influence on NOx formation. Analysis of the flow field structure reveals the regulation mechanism through which the recirculation zone morphology affects temperature distribution and flame stability. Based on these findings, a multi-parameter matching strategy is proposed, centered on optimizing the FGR rate and synergistically regulating the excess air coefficient and thermal load. This strategy provides a theoretical basis for achieving efficient and low-nitrogen operation of industrial boilers.