Scanning tunnelling microscopy has been used to study the morphology of an overlayer of ceria in contact with a TiO2(110) substrate. Two types of domains were observed after ceria deposition. An ordered ceria film covered half of the surface and high-resolution imaging suggested a near-c(6×2) relationship to the underlying TiO2(110)-(1×1). The other half of the surface comprised CeOx nanoparticles and reconstructed TiOx supported on TiO2(110)-(1×1). Exposure to a small amount of gold resulted in the formation of isolated gold atoms and small clusters on the ordered ceria film and TiO2(110)-(1×1) areas, which exhibited significant sintering at 500K and showed strong interaction between the sintered gold clusters and the domain boundaries of the ceria film. The Au/CeOx/TiO2(110) model system proved to be a good catalyst for the water–gas shift (WGS) exhibiting much higher turnover frequencies (TOFs) than Cu(111) and Pt(111) benchmarks, or the individual Au/TiO2(110) and Au/CeO2(111) systems. For Au/CeOx/TiO2(110) catalysts, there was a decrease in catalytic activity with increasing ceria coverage that correlates with a reduction in the concentration of Ce3+ formed during WGS reaction conditions.