Core–shell PdCu nanoparticles with different metal proportions were synthesized using a one-pot methodology and characterized by STEM, HRTEM, XANES and EXAFS analysis. The bimetallic nanoparticles were applied as catalysts in the Sonogashira cross-coupling reaction to investigate the mode of action of the PdCu in the reaction. The copper content directly influenced the generation of the cross-coupling product, shaping the performance of the catalyst. A quasi-homogeneous reaction pathway was evidenced by kinetics and poisoning experiments as well as XAS, HRTEM and HRMS analysis. These findings help to elucidate the mode of action of the PdCu nanocatalysts in the, as yet, unrevealed Sonogashira mechanism and the potential development of new nanocatalysts.