Metal-support interactions are frequently invoked to explain the enhanced catalytic activity of metal nanoparticles dispersed over reducible metal-oxide supports, yet the atomic scale mechanisms are rarely known. Here, we use scanning tunneling microscopy to study a Pt1-6/Fe3O4 model catalyst exposed to CO, H2, O2, and mixtures thereof, at 550 K. CO extracts lattice oxygen at the cluster perimeter to form CO2, creating large holes in the metal-oxide surface. H2 and O2 dissociate on the metal clusters and spill over onto the support. The former creates create surface hydroxyl groups, which react with the support to desorb water, while atomic oxygen reacts with Fe from the bulk to create new Fe3O4(001) islands. The presence of the Pt is crucial because it catalyses reactions that already occur on the bare iron-oxide surface, but at higher temperatures.