Objectives: N2O is widely used in the chemical industry and laboratories; however, several fire/explosion accidents have been reported in facilities that handle N2O. This study aimed (i) to experimentally investigate the lower and upper flammability limits (LFL and UFL, respectively), limit nitrous oxide concentration (LN2OC), and minimum inerting concentrations (MICs) of fuel–N2O–diluent mixtures and (ii) to computationally estimate the UFLs of fuel–N2O–diluent mixtures. Methods: Herein, methane and n-propane and nitrogen (N2), argon (Ar), and carbon dioxide (CO2) were used as fuels and diluents, respectively. The LFL, UFL, LN2OC, and MICs of the fuel–N2O–diluent mixtures were experimentally determined using a closed cylindrical vessel, and their UFLs were computationally estimated based on the laws of conservation energy and mass and adiabatic flame temperatures. Results: Flammability-limit experiments revealed the following: (i) the LFLs of the CH4–N2O–diluent and C3H8–N2O–diluent mixtures were 2.5 and 1.4 vol %, respectively, (ii) the UFLs of the CH4–N2O–diluent and C3H8–N2O–diluent mixtures were 40.5 and 24.0 vol %, respectively, (iii) a nearly linear relationship between the UFL and diluent concentration was found, and (iv) the order of MICs in N2O atmosphere was consistent with the inerting ability of the diluents. Calculations based on overall combustion reactions and the laws of energy and mass conservation using six and five chemicals successfully estimated the UFLs of the CH4–N2O–diluent and C3H8–N2O–diluent mixtures with mean absolute percentage errors of ≤2.8% and ≤4.1%, respectively. Conclusions: The semiempirical model suggested herein allows accurate estimation of the UFLs of the tested fuel–N2O–diluent mixtures. These findings would contribute to reducing accident-induced losses in the chemical industry and laboratories handling N2O.