Sensitive and non-intrusive detection of gas-phase methanol with high spatial and temporal resolution has for the first time been reported using mid-infrared degenerate four-wave mixing (IR-DFWM). IR-DFWM spectra of methanol have been successfully recorded in nitrogen-diluted gas flows at room temperature and at 300 °C, by probing ro-vibrational transitions belonging to the fundamental C–H stretching modes, ν 2 and ν 9, and the O–H stretching mode, ν 1. The detection limit of methanol vapor at room temperature and atmospheric pressure is estimated to be 250 ppm with the present setup. Potential interference from CH4 and CO2 is discussed from recorded IR-DFWM spectra of CH4 and CO2, and it was found that detection of methanol free from CH4 and CO2 interference is possible. These results show the potential of the detection of methanol with IR-DFWM for applications in both combustion and catalytic environments, such as CO2 hydrogenation and CH4 oxidation.