Efficient oxygen reduction reaction (ORR) electrocatalysts with high methanol tolerance are essential for the development of direct methanol fuel cells. Herein, a novel synthesis method is presented for the production of porous AgPd nanomushrooms with adjustable Ag/Pd atomic ratios using a seed‐mediated epitaxial etching process. These Ag 1 Pd 1 nanomushrooms display superior methanol tolerance in the ORR compared to other AgPd nanocrystals and commercial Pd/C catalysts. Specifically, the ORR activity of Ag 1 Pd 1 nanomushrooms is observed to be nine times higher than that of commercial Pd/C when tested in an O 2 ‐saturated 5 m methanol solution. Theoretical calculations suggest that the appropriate Ag/Pd atomic ratio in the nanomushrooms enables a balanced adsorption energy for both O 2 and CH 3 OH, thereby achieving enhanced ORR activity and methanol tolerance simultaneously. This research introduces a new approach to the design of efficient ORR catalysts with high methanol tolerance.