Metal nanowires are one of the potential candidates for nanostructured sensing elements used in future portable devices for chemical detection; however, the optimal methods for fabrication have yet to be fully explored. Two routes to nanowire fabrication, electron-beam lithography (EBL) and focused ion beam (FIB) etching, are studied, and their electrical and chemical sensing properties are compared. Although nanowires fabricated by both techniques exhibit ohmic conductance, I–V characterization indicates that nanowires fabricated by FIB etching exhibit abnormally high resistivity. In addition, the resistivity of nanowires fabricated by FIB etching shows very low sensitivity toward molecular adsorption, while those fabricated by EBL exhibit sensitive resistance change upon exposure to solution-phase adsorbates. The mean grain sizes of nanowires prepared by FIB etching are much smaller than those fabricated by EBL, so their resistance is dominated by grain-boundary scattering. As a result, these nanowires are much less sensitive to molecular adsorption, which mediates nanowire conduction through surface scattering. The much reduced mean grain sizes of these nanowires correlate with Ga ion damage caused during the ion milling process. Thus, even though the nanowires prepared by FIB etching can be smaller than their EBL counterparts, their reduced sensitivity to adsorption suggests that nanowires produced by EBL are preferred for chemical and biochemical sensing applications.