The finding of new metal alloyed nanocrystals (NCs) with high catalytic activity and low cost to replace PtRu NCs is a critical step toward the commercialization of fuel cells. In this work, a simple cation replacement reaction was utilized to synthesize a new type of ternary Fe1-xPtRux NCs from binary FePt NCs. The detailed structural transformation from binary FePt NCs to ternary Fe1-xPtRux NCs was analyzed by X-ray absorption spectroscopy (XAS). Ternary Fe35Pt40Ru25, Fe31Pt40Ru29, and Fe17Pt14Ru43 NCs exhibit superior catalytic ability to withstand CO poisoning in methanol oxidation reaction (MOR) than do binary NCs (FePt and J-M PtRu). Also, the Fe31Pt40Ru29 NCs had the highest alloying extent and the lowest onset potential among the ternary NCs. Furthermore, the origin for the superior CO resistance of ternary Fe1-xPtRux NCs was investigated by determining the adsorption energy of CO on the NCs' surfaces and the charge transfer from Fe/Ru to Pt using a simulation based on density functional theory. The simulation results suggested that by introducing a new metal into binary PtRu/PtFe NCs, the anti-CO poisoning ability of ternary Fe1-xPtRux NCs was greatly enhanced because the bonding of CO-Pt on the NCs' surface was weakened. Overall, our experimental and simulation results have indicated a simple route for the discovery of new metal alloyed catalysts with superior anti-CO poisoning ability and low usage of Pt and Ru for fuel cell applications.