The catalytic hydrodeoxygenation (HDO) of carbonyl oxygen in esters using H2 is an attractive method for synthesizing unsymmetrical ethers because water is theoretically the sole coproduct. Herein, we report a heterogeneous catalytic system for the selective HDO of esters to unsymmetrical ethers over a zirconium oxide-supported platinum–molybdenum catalyst (Pt–Mo/ZrO2). A wide range of esters were transformed into the corresponding unsymmetrical ethers under mild reaction conditions (0.5 MPa H2 at 100 °C). The Pt–Mo/ZrO2 catalyst was also successfully applied to the conversion of a biomass-derived triglyceride into the corresponding triether. Physicochemical characterization and control experiments revealed that cooperative catalysis between Pt nanoparticles and neighboring molybdenum oxide species on the ZrO2 surface plays a key role in the highly selective HDO of esters. This Pt–Mo/ZrO2 catalyst system offers a highly efficient strategy for synthesizing unsymmetrical ethers and broadens the scope of sustainable reaction processes.