The direct-fired supercritical carbon dioxide cycles are one of the most promising power generation methods in terms of their efficiency and environmental friendliness. Two important challenges in implementing these cycles are the high pressure (300 bar) and high CO2 dilution (>80%) in the combustor. The design and development of supercritical oxy-combustors for natural gas require accurate reaction kinetic models to predict the combustion outcomes. The presence of a small amount of impurities in natural gas and other feed streams to oxy-combustors makes these predictions even more complex. During oxy-combustion, trace amounts of nitrogen present in the oxidizer is converted to NOx and gets into the combustion chamber along with the recirculated CO2. Similarly, natural gas can contain a trace amount of ammonia and sulfurous impurities that get converted to NOx and SOx and get back into the combustion chamber with recirculated CO2. In this work, a reaction model is developed for predicting the effect of impurities such as NOx and SOx on supercritical methane combustion. The base mechanism used in this work is GRI Mech 3.0. H2S combustion chemistry is obtained from Bongartz et al. while NOx chemistry is from Konnov. The reaction model is then optimized for a pressure range of 30–300 bar using high-pressure shock tube data from the literature. It is then validated with data obtained from the literature for methane combustion, H2S oxidation, and NOx effects on ignition delay. The effect of impurities on CH4 combustion up to 16 atm is validated using NOx-doped methane studies obtained from the literature. In order to validate the model for high-pressure conditions, experiments are conducted at the UCF shock tube facility using natural gas identical mixtures with N2O as an impurity at ∼100 bar. Current results show that there is a significant change in ignition delay with the presence of impurities. A comparison is made with experimental data using the developed model and predictions are found to be in good agreement. The model developed was used to study the effect of impurities on CO formation from sCO2 combustors. It was found that NOx helps in reducing CO formation while the presence of H2S results in the formation of more CO. The reaction mechanism developed herein can also be used as a base mechanism to develop reduced mechanisms for use in CFD simulations.