Developing highly active methanol oxidation electrocatalysts with superior anti-CO poisoning capability remains a grand challenge. Herein, a simple strategy was employed to prepare distinctive PtFeIr jagged nanowires with Ir located at the shell and Pt/Fe located at the core. The Pt64Fe20Ir16 jagged nanowire possesses an optimal mass activity of 2.13 A mgPt-1 and specific activity of 4.25 mA cm−2, giving the catalyst a great edge over PtFe jagged nanowire (1.63 A mgPt-1 and 3.75 mA cm−2) and Pt/C (0.38 A mgPt-1 and 0.76 mA cm−2). The in-situ Fourier transform infrared (FTIR) spectroscopy and differential electrochemical mass spectrometry (DEMS) unravel the origin of extraordinary CO tolerance in terms of key reaction intermediates in the non-CO pathway. Density functional theory (DFT) calculations add to the body of evidence that the surface Ir incorporation transforms the selectivity from CO pathway to non-CO pathway. Meanwhile, the presence of Ir serves to optimize surface electronic structure with weakened CO binding strength. We believe this work will advance the understanding of methanol oxidation catalytic mechanism and provide some insight into structural design of efficient electrocatalysts.