The morphology and surface elemental composition of AuPd bimetallic nanoclusters are reported to be sensitive to and affected by reduced silicon defect sites and structural corrugation on SiO2/Si(100), generated by argon ion sputtering under ultrahigh vacuum (UHV) conditions. Metastable structures of the bimetallic clusters, where Au atoms are depleted from the top surface upon annealing, are stabilized by the interaction with the reduced silica sites, as indicated from CO temperature programmed desorption (TPD) titration measurements. Acetylene conversion to ethylene and benzene has been studied as a probe reaction, revealing the modification of selectivity and reactivity enhancement in addition to improved thermal stability on substrates rich in reduced-silica sites. These observations suggest that these unique sites play an important role in anchoring thermodynamically metastable conformations of supported AuPd bimetallic catalysts and dictate their high-temperature activity.