In dual-fuel engines, diesel is typically used to initiate the ignition of methanol, resulting in a turbulent spray flame. However, the lack of skeletal or reduced mechanisms for methanol/n-heptane blends limits the further research of dual-fuel combustion. Therefore, a skeletal methanol/n-heptane mechanism including 52 species and 182 reactions was proposed based on the decoupling method. Firstly, it was validated by the recent experiments for blends and compared with several mechanisms. Good agreement between the predicted and measured results was obtained in terms of the ignition delay time, laminar flame speed, and species distributions for pure n-heptane and methanol as well as blends. The new mechanism shows improvements on the negative temperature coefficient (NTC) behavior and the low-temperature ignition for blends compared with other mechanisms. Secondly, the effect of methanol on n-heptane decomposition was investigated based on kinetic analysis. Results showed that methanol competes OH with n-heptane at low temperatures, mainly prolonging the second-stage ignition process. At high temperatures, more HO2 was produced via CH3OH→CH2OH→CH2O + HO2. The existence of methanol also removes the NTC regime toward lower temperatures at intermediate temperatures. Methanol/n-heptane dual fuels no longer exhibit NTC behaviors with high concentration methanol.