Enhancing the catalytic oxidation activity of metal oxides has become a prominent focus for improving gas sensing performance. However, the optimisation of the catalytic activity of metal oxides via lattice oxygen activation for enhanced gas sensing has been rarely reported. Herein, we developed a Pt single-atom-loaded CuO catalyst for enhanced acetone sensing, achieving a response value of 4.9 (20 ppm acetone), outperforming most reported CuO-based acetone sensors. The superior acetone sensing performance is attributed to the catalytic oxidation of acetone by CuO via the Mars–van Krevelen (MvK) mechanism, differing from the conventional surface-adsorbed oxygen mechanism. During the sensing process, acetone molecules are oxidised into intermediates (*COOCH3 and *HCOO), and subsequently to CO2 and H2O, wherein the lattice oxygens in CuO serve as catalytic sites, which are regenerated by O2 in the background gases. Interestingly, the loading of Pt single atoms, accompanied by strong metal‒support interaction, activates the surface lattice oxygen on CuO, resulting in a decreased formation energy for oxygen vacancies, increased adsorption energy for O2, and subsequently, enhanced participation of lattice oxygen in the sensing process and improved acetone sensing performance. Our research contributes to advancements in the design of sensing materials and the understanding of gas-sensing mechanisms.