Metallenes are an emerging class of two-dimensional (2D) material with outstanding potential in electrocatalysis. Herein, we present a new PdMoSb trimetallene produced by a facile wet-chemistry procedure and tested for the alcohol oxidation reaction. PdMoSb shows an extremely high Pd utilization and superior performance toward ethanol, methanol, and glycerol electro-oxidation compared with PdMo and commercial Pd/C catalysts. Experimental results and density functional theory calculations reveal that the enhanced activity relies not only on the high surface area that characterizes the ultrathin 2D metallene structure, but also on the particular electronic configuration of Sb. Sb facilitates OH⁻ adsorption in the reactive-intermediate pathway and strongly enhances the CO tolerance in the poisoning-intermediate pathway for alcohol oxidation. The excellent alcohol oxidation performance of PdMoSb trimetallene demonstrates the high potential of multimetallenes in the field of electrocatalysis.