Abstract: The development of deep and ultra-deep unconventional oil and gas fracturing imposes higher requirements on the mechanical properties and sealing integrity of cement sheaths under cyclic load in high-temperature environments. There is an urgent need to clarify the variation patterns of cement stone’s mechanical properties under high-temperature conditions to support the enhancement of cement sheath sealing capacity in deep oil and gas wells. By applying mechanical loading, scanning electron microscopy (SEM), and nuclear magnetic resonance (NMR) tests to investigate the macroscopic mechanical performance changes, plastic residual strain changes, and the evolution of the microscopic pore structure of cement stone under high-temperature environments and cyclic loads, the evolution laws of the microstructure of cement stone were revealed, and the constitutive relationship of cumulative plastic residual strain of cement stone was constructed. The research results show that a higher curing temperature means a larger average pore size and porosity of the cement stone and a lower elastic modulus of the cement stone. At the same time, the plastic residual strain of the cement stone after loading increases. With the increase in the number of cycles, the hysteresis loop curve formed by cyclic loading and unloading becomes increasingly dense from sparse. The results of the microstructure mechanical analysis show that the collapse and compression of the elongated pores (b/a>100) in the cement stone under cyclic loading are the main causes of the plastic residual strain of the cement stone. In deep and high-temperature underground environments, the cement sheath’s compactness can be enhanced through particle grading and nano-particle materials, while the pore size and porosity can be reduced to minimize the microscopic pore deterioration and macroscopic residual strain caused by cyclic loads. The research results have significant guiding significance for optimizing the cement slurry system and well cementing techniques that can enhance the sealing ability of the cement sheath in high-temperature environments.