Exploring the interactions of oxygen with defective oxide is of importance to understand the microscopic process and performance of ZnO-based oxygen sensors. The interactions of environmental oxygen with vacuum-annealed defective ZnO have been studied by electrical methods, vacuum Fourier transform infrared spectroscopy, and in situ adsorption experiments. It was found that the vacuum-annealed defective ZnO exhibits varied electrical response at different temperatures, which, by vacuum IR investigation, was ascribed to the subtle balance between formation of oxygen vacancies and their interactions with environmental oxygen. Further studies showed that two microscopic steps including surface adsorption and bulk diffusion were dominating the interactions between defective ZnO and environmental oxygen, and the corresponding apparent activation energies were estimated to be 0.093 and 0.67eV through in situ adsorption experiments. The quite low activation barrier of oxygen adsorption on the defective ZnO was proposed to be responsible for the extreme high sensitivity of ZnO-based oxygen sensors.