Catalytic conversion of ethanol to 1-butanol was studied over MgO–Al2O3mixed oxide-based catalysts. Relationships between acid-base and catalytic properties and the effect of active metal on the hydrogen transfer reaction steps were investigated. The acid-base properties were studied by temperature-programmed desorption of CO2and NH3and by the FT-IR spectroscopic examination of adsorbed pyridine. Dispersion of the metal promoter (Pd, Pt, Ru, Ni) was determined by CO pulse chemisorption. The ethanol coupling reaction was studied using a flow-through microreactor system, He or H2carrier gas, WHSV = 1gEtOH·gcat.−1·h−1, at 21 bar, and 200–350 °C. Formation and transformation of surface species under catalytic conditions were studied by DRIFT spectroscopy. The highest butanol selectivity and yield was observed when the MgO–Al2O3catalyst contained a relatively high amount of strong-base and medium-strong Lewis acid sites. The presence of metal improved the activity both in He and H2; however, the butanol selectivity significantly decreased at temperatures ≥ 300 °C due to acceleration of undesired side reactions. DRIFT spectroscopic results showed that the active metal promoted H-transfer from H2over the narrow temperature range of 200–250 °C, where the equilibrium allowed significant concentrations of both dehydrogenated and hydrogenated products.