The oxidation of CO is the archetypal heterogeneous catalytic reaction and plays a central role in the advancement of fundamental studies, the control of automobile emissions, and industrial oxidation reactions. Copper-based catalysts were the first catalysts that were reported to enable the oxidation of CO at room temperature, but a lack of stability at the elevated reaction temperatures that are used in automobile catalytic converters, in particular the loss of the most reactive Cu+ cations, leads to their deactivation. Using a combined experimental and theoretical approach, it is shown how the incorporation of titanium cations in a Cu2O film leads to the formation of a stable mixed-metal oxide with a Cu+ terminated surface that is highly active for CO oxidation.