Argon (Ar), nitrogen (N2) and carbon dioxide (CO2), present in exhaust gas recirculation (EGR) and air, are common atomic, diatomic and polyatomic inert gases, separately. As dilution gases, they are always added into the intake charge to reduce nitrogen oxides (NOx) emissions, directly or along with EGR and air. This paper presents the effects of Ar, N2 and CO2 on mixture properties, combustion, thermal efficiency and NOx emissions of pilot-ignited natural gas engines. Thermodynamic properties of the air-dilution gas mixture with increasing dilution gases, including density, gas constant, specific heat ratio, specific heat capacity, heat capacity and thermal diffusivity, were analyzed theoretically using thermodynamic relations and ideal gas equations based on experimental results. The thermal and diluent effects of dilution gases on NOx emissions were investigated based on Arrhenius Law and Zeldovich Mechanism, experimentally and theoretically. The experiments were arranged based on an electronically controlled heavy-duty, 6-cylinder, turbocharged, pilot-ignited natural gas engine. The resulted show that adding different inert gases into the intake charge had different influences on the thermodynamic properties of the air-dilution gas mixture. No great change in combustion phase was found with increasing dilution ratio (DR) of Ar, while the flame development duration increased significantly and CA50 moved far away from combustion top dead center (TDC) obviously with increasing DR for both of N2 and CO2. Adding Ar was superior in maintaining high thermal efficiencies than CO2 and N2, but adding CO2 was superior in maintaining low NOx emissions than N2 and Ar. In addition, the mechanisms of reducing NOx emissions were different for different dilution gases.