Le Chatelier’s rule is a well-known method for estimating the fuel mixture flammability limit, and this empirical equation works Best for estimating the lower flammability limits. In this paper, a detailed derivation was conducted on lower flammability limits to shed light on the inherent principle residing in this rule. By assuming a constant flame temperature for pure fuels and mixtures during flame propagation, a theoretical evaluation of Le Chatelier’s rule was presented. Results showed that this rule can be extended to non-ambient conditions for lower flammability limit estimations, particularly when the initial fuel/air reaction system is at non-extreme conditions. Meanwhile, when fuel mixture is diluted with inert gases, or at varied oxygen concentrations, Le Chatelier’s rule still works at lower flammability limit conditions. Unlike the lower flammability limit, generalizations of this rule at upper flammability limits turn out to be impossible when using the same reaction mechanism. This is because of the high complexity of combustion kinetics and dynamic variation of convection flow at the upper flammability limits. Moreover, thermal control is a generally accepted principle for governing the combustion reaction at the lower flammability limit; however, we found that this condition does not necessarily valid for all fuels, such as hydrogen. Finally, a modified Le Chatelier’s mixing rule was proposed with the relaxation of constant flame temperature. The findings from this study can be used as guidelines to maximize safety in the process design and operational procedures involving flammable chemicals.