The development of cost-effective methanol oxidation reaction (MOR) catalysts with a high activity and stability is highly desirable for direct methanol fuel cells. In this study, the structurally ordered PtSn intermetallic nanoparticles supported on Sb-doped SnO2 (ATO) have been successfully synthesized in ethylene glycol (EG) solution at 200 °C. Pt NPs were firstly formed on ATO, followed by the transformation from Pt into hexagonal PtSn on the surface of ATO. The obtained structurally ordered PtSn intermetallic NPs supported on ATO demonstrate significantly enhanced MOR activity and durability in comparison with commercial Pt/C. Our PtSn intermetallic NPs supported on ATO show a MOR activity 4.1 times higher than that of commercial Pt/C catalysts. Accelerated durability tests indicate that the commercial Pt/C catalysts lose about 50% of their initial current density after 500 cycles while the Pt/ATO-200-3 h catalyst loses only about 15% of its initial current density. Our PtSn intermetallic NPs supported on ATO are also found to have higher CO tolerance than commercial Pt/C. This work demonstrates an important strategy to rationally design high-performance structurally ordered Pt-based intermetallic NP catalysts for fuel cells and other applications.