The electrochemical oxidation of methanol is a crucial catalytic reaction in direct methanol fuel cells (DMFCs). Platinum (Pt) or Pt-alloy electrocatalysts have dominated the space, especially in acidic conditions, and different design strategies are needed to achieve both high specific and mass activities. Herein, we comprehensively developed a system of cobalt−platinum−ruthenium nanoparticles within three-dimensional nitrogen-doped porous carbon (Co−Pt− Ru/NC) as an efficient methanol oxidation reaction (MOR) catalyst and investigated different factors such as Pt loading and acid treatment. We found that the intermediate Pt loading displayed MOR activity as low as 0.3 V RHE (versus the reversible hydrogen electrode) and exhibited the highest specific activity (2.1 ± 0.2 mA cm Pt −2) and mass activity (0.28 ± 0.06 A mg Pt+Ru −1 ) at 0.6 V RHE , which is 4.4 times and 3.9 times higher than the commercial PtRu/C catalysts, respectively. Furthermore, the catalytic activity remains nearly unchanged in acid-treated catalysts after cobalt is partially dissolved in acidic conditions. Through density functional theory calculations of the MOR on our catalyst surface, the enhanced activity was found to originate from cobalt weakening CO adsorption on Pt sites, while simultaneously facilitating OH formation on Ru sites, effectively lowering the energy barrier for the rate-determining step in the MOR and showing promising potential for DMFCs.