Three Ag-CeO2/SiO2 catalysts were prepared by different methods, namely, sequential impregnation, co-impregnation and impregnation of pre-reduced CeO2/SiO2 and are tested in the oxidative dehydrogenation of ethanol. The order of introduction of silver and ceria precursors is found to influence the catalytic activity that increases in the order of preparation method: sequential impregnation < co-impregnation < impregnation of pre-reduced CeO2/SiO2. Results of TPR-H2, TEM HR, XPS and Raman characterizations show the best interfacial Ag–CeO2 interaction and highest defectiveness of CeO2 nanoparticles in the catalyst prepared by impregnation of pre-reduced CeO2/SiO2. A correlation between Ag–CeO2 interaction and catalytic activity is found in the series of Ag-CeO2/SiO2 catalysts depending on the preparation method. Enhanced Ag–CeO2 interfacial interaction leads to increased activity in oxidative dehydrogenation of ethanol.