Antiferroelectric (AFE) ZrO2-based devices are anticipated to exhibit superior endurance properties in comparison to their ferroelectric (FE) counterparts. Nevertheless, the underlying mechanisms of AFE devices remain elusive. In this study, guided by the dynamic evolution of oxygen vacancies (Vo), we reveal three kinds of fatigue in AFE HfxZr1−xO2 (HZO) during uni-directional cycling. The first mechanism is related to the interfacial Vo charge trapping, which accelerates the switching from the P↓↑ state to the P↓↓ state, leading to extrinsic fatigue, and is demonstrated by electrical stress measurements. The other two mechanisms are Vo-related AFE to FE phase transition (PT) and Vo localization inside the HZO films, which are supported by the first-principles calculations. The highest polarization switching barrier occurs when Vo is localized at the tetra-coordinated oxygen sites inside HZO films. This means that tetra-coordinated Vo accumulation leads to less polarization switching, resulting in AFE to FE PT and Vo localization induced fatigue, i.e., intrinsic fatigue. This work reveals the dynamic evolution of Vo during cycling and its impact on AFE properties, paving the way for developing more durable AFE ZrO2-based devices and contributing to the emergence of diverse recovery methods in the future.