Tuning metal–support interactions (MSIs) is an important strategy in heterogeneous catalysis to realize the desirable metal dispersion and redox ability of metal catalysts. Herein, we use pre-reduced Co3O4 nanowires (Co-NWs) in situ grown on monolithic Ni foam substrates to support Ag catalysts (Ag/Co-NW-R) for soot combustion. The macroporous structure of Ni foam with crossed Co3O4 nanowires remarkably increases the soot–catalyst contact efficiency. Our characterization results demonstrate that Ag species exist as Ag0 because of the equation Ag+ + Co2+ = Ag0 + Co3+, and the pre-reduction treatment enhances interactions between Ag and Co3O4. The number of active oxygen species on the Ag-loaded catalysts is approximately twice that on the supports, demonstrating the significant role of Ag sites in generating active oxygen species. Additionally, the strengthened MSI on Ag/Co-NW-R further improves this number by increasing metal dispersion and the intrinsic activity determined by the turnover frequency of these oxygen species for soot oxidation compared with the catalyst without pre-reduction of Co-NW (Ag/Co-NW). In addition to high activity, Ag/Co-NW-R exhibits high catalytic stability and water resistance. The strategy used in this work might be applicable in related catalytic systems.