Composition optimization of the ternary Pt–Ru–Cu system for the methanol electro-oxidation reaction (MOR) was performed by combinatorial synthesis and high-throughput screening methods. A thin film library of the Pt–Ru–Cu system was prepared by a sputtering system to generate 63 different compositions. The compositions were characterized in parallel by a multichannel multielectrode analyzer. The highest MOR activity was observed for the Pt66Ru17Cu17 composition. The Pt66Ru17Cu17/C composition was synthesized and characterized as a powder catalyst to verify the performance of this new composition. During cyclic voltammetry tests, the Pt66Ru17Cu17/C catalyst showed less dissolution and irreversible oxidation of Ru than a Pt50Ru50/C catalyst, with increasing number of cycles. In MOR activity measurement experiments, the Pt66Ru17Cu17/C catalyst exhibited 26 and 86% higher activities in cyclic and chronoamperometric tests, respectively, than those of the Pt50Ru50/C catalyst.