Direct ethanol fuel cells (DEFCs) have been considered as future power devices for many portable applications. The ethanol oxidation reaction (EOR), that is, a multielectron process, suffers from low efficiency owing to the high selectivity to the 4e− pathway (C2 pathway) and low selectivity to the 12e− pathway (C1 pathway). The preparation of efficient catalysts with high C1 pathway selectivity is regarded as a promising and fascinating field. Herein, we first advance a one-pot synthesis of 3D PdAg superstructures (SSs) with a hollow interior and ultrathin nanosheet shell. PdAg SSs achieve a mass activity of 5.27 A mg−1 for the alkaline EOR and a Faraday efficiency of 22.7 % for the C1 pathway, which is 5.7 and 7.5 times higher than that of commercial Pd/C, respectively. Mechanism studies confirm that the construction of the Pd-Ag system greatly facilitates the oxidation of the C1 intermediates (*CH3 and *CO) and enhances the CC bond cleavage ability of the catalyst. This work not only highlights an active Pd-based catalyst for the selective EOR, but also sheds light on the formation of 3D open nanostructure via self-assembly of 2D nanosheets.