Through an interplay between scanning tunneling microscopy (STM) and density functional theory (DFT) calculations, we show that bridging oxygen vacancies are the active nucleation sites for Au clusters on the rutile TiO2(110) surface. We find that a direct correlation exists between a decrease in density of vacancies and the amount of Au deposited. From the DFT calculations we find that the oxygen vacancy is indeed the strongest Au binding site. We show both experimentally and theoretically that a single oxygen vacancy can bind 3 Au atoms on average. In view of the presented results, a new growth model for the TiO2(110) system involving vacancy-cluster complex diffusion is presented.