Even though substantial attention has been focused on exploring promising palladium-based catalysts, the creation of electrocatalysts with simultaneous high activity and reduced cost for fuel cell reactions remains a challenge. Here, we report on the design and construction of a new class of three-dimensional (3D) palladium-rhodium (PdRh) nanosheet assembly (NSA) catalysts through a seed-mediated growth method. Interestingly, the well-defined NSAs with optimized electronic structures and highly open 3D structures exhibit greatly enhanced electrocatalytic activity toward the methanol oxidation reaction (MOR). In particular, optimized PdRh NSAs have a mass activity of 1672.7 mA mg for the MOR, 5.4 times higher than that of commercial Pd/C catalysts (303.8 mA mg). More importantly, these PdRh NSAs also display improved MOR stability, with stable high electrocatalytic performance for more than 250 potential cycles.