Copper oxide (CuO) nanoparticles have received considerable interest as active and inexpensive catalysts for various gas–solid reactions. The CuO reducibility and surface reactivity are of crucial importance for the high catalytic activity. Herein, we demonstrate that the reducibility and stability of CuO nanoparticles can be controlled and tailored for the high catalytic activity of CO oxidation. The synthesized CuO nanoparticles possessed enhanced reducibility in CO atmosphere at lower reduction temperature of 126 °C compared to 284 °C for that of reference CuO particles. Moreover, the CuO catalysts with tailored reducibility demonstrated a reaction rate of 35 μmol s⁻¹ g⁻¹ and an apparent activation energy of 75 kJ mol⁻¹. Furthermore, the tailored catalysts exhibited excellent long-term stability for CO oxidation for up to 48 h on stream. These readily-reducible CuO nanoparticles could serve as efficient, inexpensive and durable catalysts for CO oxidation at low temperatures.