Mechanistic control is a powerful means for manufacturing specific shapes of metal nanostructures and optimizing their performance in a variety of applications. Thus, we successfully synthesized multimetallic nanoplates (PtAgBiCo and PtAgBi) by combining the concepts of crystal symmetry, oxidative etching and seed ratio, and tuned their activity, stability and methanol tolerance, as well as Pt utilization, for the oxygen reduction reaction in direct methanol fuel cells. Systematic studies reveal that the formation of PtAgBiCo triangular nanoplates with a high morphological yield (>90%) can be achieved by crystallinity alteration, while electrochemical measurements indicate that the PtAgBiCo nanoplates have superior electrocatalytic activity towards the oxygen reduction reaction. The specific and mass activity of the PtAgBiCo nanoplates are 8 and 5 times greater than that of the commercial Pt/C catalyst, respectively. In addition, the tetrametallic PtAgBiCo nanoplates exhibit a more positive half-wave potential for the oxygen reduction reaction and possess an excellent methanol tolerance limit compared with the commercial Pt/C catalyst.