Currently, the depletion of fossil fuels has become a pressing issue for society, and one potential solution is the conversion of ethanol, a vital biomass derivative, into high-value chemicals using tandem reactions based on anaerobic dehydrogenation processes. Here, we developed a new copper nanocatalyst supported on a defect-rich MnO x matrix, fabricated by a modified coprecipitation method using a microliquid-film (MLF) reactor. By enhancing the micromixing of Mn and Cu ions in the synthesis solution, the use of the MLF reactor promoted the dispersion of copper particles with favorable interfacial Cu + −O−Mn structures and the formation of defect-rich MnO x support with abundant oxygen vacancies. The as-fabricated Cu/MnO x catalyst delivered a higher yield of acetaldehyde and greater structural stability, compared to two Cu-based catalysts produced using traditional impregnation and coprecipitation methods. Surface defective oxygen vacancies and interfacial Cu + −O−Mn structures were found to effectively facilitate the activation adsorption of ethanol and stabilize the formed ethoxy intermediate, improving the dehydrogenation of ethanol to produce acetaldehyde. This work presents a novel synthesis strategy for supported metal catalysts, which enables the creation of active surface-interface structures, resulting in exceptional catalytic properties for use in various advanced catalytic processes.