One-dimensional titanium dioxide nanorod (TNR)-supported Cu catalysts (2.5 wt.%-12.5 wt.%) were synthesized using deposition-precipitation. X-ray photoelectron spectroscopy, temperature programmed reduction and CO chemisorption measurements showed that Cu doping over TNR offered metal-support interactions and interfacial active sites that had a profound impact on the catalytic performance. The role of the Cu-TNR interface was investigated by comparing the catalytic activity of Cu-TNR catalysts with that of pure CuO nanoparticles in CO oxidation. The presence of highly dispersed copper species, a high number of interfacial active sites, CO adsorption capacity and surface/lattice oxygen were found to be responsible for the excellent activity of 7.5Cu-TNR (i.e., Cu loading of 7.5 wt.% on TNR). Moreover, the Cu-TNR catalysts followed the Langmuir-Hinshelwood reaction mechanism with 7.5Cu-TNR, exhibiting an apparent activation energy of 44.7 kJ/mol. The TNR-supported Cu catalyst gave the highest interfacial catalytic activity in medium-temperature CO oxidation (120-240 °C) compared to other commonly used supports, including titanium dioxide nanoparticles (TiO₂-P25), silica (SiO₂) and alumina (Al₂O₃) in which copper species were nonhomogeneously dispersed. This study confirms that medium-temperature CO oxidation is highly sensitive to the morphology and structure of the supporting material.