The advancement in catalytic processes utilizing sustainable raw materials, such as bioethanol, represents a key scientific challenge in this century. One potential approach to producing 1-butanol, a compound primarily obtained from petroleum-derived sources, is through the Guerbet reaction. For this transformation, various multifunctional catalysts have been explored, some of which incorporate Cu and/or Ni nanoparticles that facilitate hydrogenation and dehydrogenation reactions, along with magnesium oxide, which provides the necessary acid/base functionality. To promote nanoparticle formation and maximize the exposed active surface area, high-surface-area graphite (HSAG), a hydrophobic and inert support material, emerges as a promising candidate. In this study, different catalyst formulations containing these components were tested under moderate reaction conditions, at temperatures between 440 and 580 K and a pressure of 50 bar. A strong correlation was observed between butanol selectivity and the presence of medium–high strength basic sites, complemented by moderate acidity. Furthermore, optimizing the copper and nickel loadings to 4 wt.% Cu and 1 wt.% Ni significantly minimized the formation of unwanted byproducts. The highest butanol selectivity (44%) was achieved using a 4Cu1Ni-Mg/HSAG catalyst, which had been pretreated in helium at 723 K before H2 reduction, yielding approximately 9% 1-butanol.