As a plethora of different unsaturated oxygenates is produced from the pyrolysis of biomass into bio-oil, understanding the role of competitive adsorption in catalytic upgrading is essential. To this end, the relative reactivities of representative molecules of key families within a single feed mixture were examined through reaction testing and in situ infrared spectroscopy characterization. The influence of the support (silica, ceria, zirconia, titania, and niobia) on the rate of elimination of hydroxyl and methoxy groups was evaluated on single compounds (phenol, m-cresol, and anisole) and binary mixtures (phenol/anisole and m-cresol/anisole). The removal of hydroxyl groups depends significantly on the support type. Pd supported on SiO2 and CeO2 favored ring hydrogenation resulting in the production of oxygenated products such as cyclohexanone/3-methylacylohexanone. The use of ZrO2, TiO2, and Nb2O5 as supports promotes the formation of benzene/toluene by hydrogenation of the carbonyl group of the tautomer intermediate formed or even direct deoxygenation. The reaction pathways for removal of methoxy groups also depend on the support. The demethylation route that yields methane and phenol and its further deoxygenation to benzene is proposed to take place over all catalysts, except on Pd/Nb2O5. Due to the superior oxophilicity of Nb cations, the niobia-supported catalyst greatly favors the direct deoxygenation, with formation of benzene and methanol (demethoxylation). The reaction with binary mixtures of phenol/anisole and m-cresol/anisole revealed that the hydroxyl groups react preferentially. Insight into the mode and strength of adsorption of the different molecules on the catalyst surface was obtained by DRIFTS analysis upon adsorption and desorption. The results indicate that under the HDO reaction conditions investigated phenol and m-cresol seem to adsorb more strongly on the catalyst surface and react more readily than anisole. Thus, this study shows that competitive adsorption is a predominant factor impacting product selectivity.