Pd/Al2O3 and Pd–M/Al2O3 catalysts (M = Au, Ag, Cu, Ce, Fe, Ni, Co, Zn) were obtained by ion exchange and impregnation. Pd/Al2O3 had high initial activity in the conversion of ethanol into α-alcohols, but lost 90% of its activity after 10 h of operation because of deactivation caused by the chemisorption of the by-product (CO) on Pd atoms. Modification of Pd with gold or silver led to an increase in the rate of Pd deactivation. As a result, the Pd–Au and Pd–Ag systems were less active and stable. In contrast, the Pd–Fe, Pd–Co, Pd–Ni, Pd–Cu, Pd–Zn, and Pd–Ce systems exhibited higher resistance to CO poisoning than Pd and demonstrated high activity and stability. The observed tendencies in the catalytic action of the mono- and bimetallic systems were explained within the framework of the d band model proposed by Hammer and Norskov. Pd–Cu/Al2O3 was most effective in the target process; it is not poisoned by CO and allows ethanol conversion into α-alcohols at 95% selectivity, while the time of its stable operation is at least 100 h. The structure of the Pd–Cu catalytic system was studied by TEM, EDA, XPS, TPR-H2, and TPD-NH3. A model of active catalyst sites was proposed.