Offshore high-temperature and high-pressure wells frequently experience integrity failures due to changes in temperature and pressure, causing issues such as annular pressure and wellhead uplift. A full-scale “production casing-cement sheath-technical casing” combination experimental device is developed based on the typical wellbore structure of high temperature and high pressure wells. Tests on the cement sheath’s interface bonding integrity were conducted under three different alternating thermal loads, comparing differences between small-scale and full-scale physical experimental results. The study elucidated the degradation behaviour and mechanism of the cement sheath interface bonding under alternating thermal loads. The results show that high temperature and alternating thermal loads have a significant negative impact on the bonding performance of the cement sheath interface, with the degree of failure increasing with higher temperatures and more frequent alternations. Before the bonding failure of the cement sheath interface, the alternating thermal load mainly damages the chemical bonding between the casing and cement sheath interface until detachment occurs, creating micro-annular gaps. The formation and expansion of micro-annular gaps are the main reasons for decreased interfacial friction. There are certain differences between small-scale and full-scale physical experimental results, which make it difficult to accurately describe the mechanical properties of the cement sheath interface under actual conditions. The research findings can provide a basis and reference for the design of cement slurry in well cementing for high-temperature and high-pressure wells, management of wellbore integrity, and prediction and management of wellhead uplift.