A ReO x -promoted Rh/C catalyst is shown to be selective in the hydrogenolysis of secondary C–O bonds for a broad range of cyclic ethers and polyols, these being important classes of compounds in biomass-derived feedstocks. Experimentally observed reactivity trends, NH3 temperature-programmed desorption (TPD) profiles, and results from theoretical calculations based on density functional theory (DFT) are consistent with the hypothesis of a bifunctional catalyst that facilitates selective hydrogenolysis of C–O bonds by acid-catalyzed ring-opening and dehydration reactions coupled with metal-catalyzed hydrogenation. The presence of surface acid sites on 4 wt % Rh–ReO x /C (1:0.5) was confirmed by NH3 TPD, and the estimated acid site density and standard enthalpy of NH3 adsorption were 40 μmol g–1 and −100 kJ mol–1, respectively. Results from DFT calculations suggest that hydroxyl groups on rhenium atoms associated with rhodium are acidic, due to the strong binding of oxygen atoms by rhenium, and these groups are likely responsible for proton donation leading to the formation of carbenium ion transition states. Accordingly, the observed reactivity trends are consistent with the stabilization of resulting carbenium ion structures that form upon ring-opening or dehydration. The presence of hydroxyl groups that reside α to carbon in the C–O bond undergoing scission can form oxocarbenium ion intermediates that significantly stabilize the resulting transition states. The mechanistic insights from this work may be extended to provide a general description of a new class of bifunctional heterogeneous catalysts, based on the combination of a highly reducible metal with an oxophilic metal, for the selective C–O hydrogenolysis of biomass-derived feedstocks.