Photoactivation is a promising approach for room-temperature gas sensing with metal oxide semiconductors. For room-temperature methane (CH4) gas sensors, it is highly desirable to develop sensing materials with high photocatalytic CH4 oxidation activity so as to improve their UV-activated CH4 sensing performance. Herein, we reported that mesoporous ZnO nanosheets with rich surface oxygen vacancies (VO) exhibited enhanced CH4-sensing properties under UV illumination at room temperature. The VO-enriched mesoporous ZnO nanosheets were fabricated via a low-temperature thermal phase transformation route. Under UV irradiation, the VO-rich ZnO nanosheets demonstrated a response of 62 % to 0.1 % CH4, about 4.7 times higher than that of VO-deficient commercial ZnO nanoparticles. The improved CH4 sensing capacity of the porous ZnO nanosheets under UV illumination was correlated to their enhanced photocatalytic oxidation activity of CH4 induced by surface VO. The in-situelectron paramagnetic resonance and O2 temperature programmed desorption analysis indicated that the generation of Zn+/O− active centers and active oxygen species could be promoted by the rich surface VO on mesoporous ZnO nanosheets. Furthermore, the density functional theory calculations suggested that VO could improve the surface charge density of ZnO and lower the Gibbs free energy for the CH4 activation on the ZnO surface.