In the present study, the catalytic coupling of ethanol into 1-butanol through the Guerbet reaction was studied in a fixed bed reactor over different catalytic systems based on Cu and/or Ni as a hydrogenating/dehydrogenating components, and manganese oxide incorporating acid/base properties over a carbonaceous support, high surface area graphite (HSAG). The catalysts were prepared by wetness impregnation of the support with the corresponding metal nitrates and the resulting material was then reduced in-situ with hydrogen at 573 K for 1 h before reaction. The catalysts were characterized by X-ray diffraction (XRD), temperature-programmed reduction (TPR), specific surface area, NH3 temperature-programmed desorption, CO2 chemisorption, transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). From all these techniques it can be deduced that the dimensions of the catalytic ingredients (Cu, Ni, Mn) are in the nanometric scale and homogeneously dispersed on the support. The reactions were performed in a continuous-flow fixed-bed reactor in gas phase with these bifunctional catalysts at 503 K and 50 bar using a stream of helium and ethanol. The bimetallic catalyst 2.5Cu2.5Ni-Mn/HSAG, treated in helium at 723 K prior reduction with hydrogen, exhibited the best catalytic performance in terms of 1-butanol selectivity (39%), presumably due to the synergetic effect of the weak strength acid sites and the strong base sites related to manganese oxide and the Cu-Ni nanoparticles.