Abstract: A microannulus (MA) is the primary reason for sustained casing pressure in multi-stage fractured-shale gas wells. However, the effect of the casing eccentricity on the long horizontal section has not been considered. In this study, a full-scale integrity tester for cement sheaths is adopted to measure the cumulative plastic deformation. Numerical models are applied to evaluate the development of the cumulative plastic deformation and quantify the MA width considering casing centralization and eccentricity in the context of multiple loading and unloading cycles. Subsequently, the influences of the eccentricity distance and angle, cement-sheath mechanical variables, and different well depths on the cumulative sheath plastic deformation and sheath MA development are explored. The research results demonstrate that casing eccentricity significantly increases the cumulative sheath plastic deformation compared with that of the casing-centered condition. Consequently, the risk of sealing integrity failure increases. The accumulated plastic deformation increases when the eccentricity distance increases. In contrast, the initial plastic deformation increases as the eccentricity angle increases. However, the cumulative plastic deformation decreases after a specific loading and unloading cycle count. Affected by the coupled influence of the internal casing pressure and fracturing stages, the width of the MA in the horizontal section increased from the toe to the heel, and the casing eccentricity significantly increased the MA width at each stage, thus increasing the risk of gas channeling. Finally, an engineering case is considered to study the influence of casing eccentricity. The results show that cement slurries that form low and high elastic moduli can be applied to form a cement sheath when the fracturing stage is lower or higher than a specific value, respectively. The results of this study offer theoretical references and engineering support for the integrity control of cement sheath sealing.