The catalytic deoxygenation of biomass fast pyrolysis vapors offers a promising route for the sustainable production of liquid transportation fuels. However, a clear understanding of the mechanistic details involved in this process has yet to be achieved, and questions remain regarding the role of the catalyst support and the influence of reaction conditions. In order to gain insight into these questions, the deoxygenation of m-cresol was investigated over Pt/C and Pt/TiO<
sub>
2<
/sub>
catalysts using experimental and computational techniques. The performance of each catalyst was evaluated in a packed-bed reactor under two conditions (523 K, 2.0 MPa and 623 K, 0.5 MPa), and the energetics of the ring hydrogenation, direct deoxygenation, and tautomerization mechanisms were calculated over hydrogen-covered Pt(111) and oxygen vacancies on the surface of TiO<
sub>
2<
/sub>
(101). Over Pt(111), ring hydrogenation to 3-methylcyclohexanone and 3-methylcyclohexanol was found to be the most energetically favorable pathway. Over TiO<
sub>
2<
/sub>
(101), tautomerization and direct deoxygenation to toluene were identified as additional energetically favorable routes. These calculations are consistent with the experimental data, in which Pt/TiO<
sub>
2<
/sub>
was more active on a metal site basis and exhibited higher selectivity to toluene at 623 K relative to Pt/C. On the basis of these results, it is likely that the reactivity of Pt/TiO<
sub>
2<
/sub>
and Pt/C is driven by the metallic phase at 523 K, while contributions from the TiO<
sub>
2<
/sub>
support enhance deoxygenation at 623 K. These results highlight the synergistic effects between hydrogenation catalysts and reducible metal oxide supports and provide insight into the reaction pathways responsible for their enhanced deoxygenation performance.