The in-situ conversion of medium-low maturity shale oil requires long-term heating of the reservoir to temperatures exceeding 350 ℃ to achieve organic matter pyrolysis. The high-temperature environment poses severe challenges to the structural integrity of the heating wellbore. While existing research has primarily focused on improving heating efficiency and conversion rates, insufficient attention has been paid to the mechanical response and safety of electrically heated wellbores under non-uniform thermal loads. To address the asymmetric heating issue caused by the eccentricity of electric heaters against the casing wall in horizontal sections, a transient heat transfer model of the wellbore-cement-formation system was established, and the evolution of the temperature field under eccentric heating conditions was revealed. Furthermore, a thermo-mechanical coupling theoretical model was developed to analyze the dynamic distribution characteristics of casing thermal stress and thermal displacement, with emphasis placed on comparing the mechanical response differences of the wellbore under concentric and eccentric heating conditions. The results indicate that heater eccentricity against the casing wall is the key factor determining wellbore safety. Eccentric heating induces localized “hot spots” on the lower outer wall of the casing, where the thermal stress is increased by more than 30% compared to the upper outer wall, and the safety factor is reduced by 25% to 40%. The sensitivity analysis indicates that the thermal expansion coefficient, heating temperature, eccentricity, casing wall thickness, and thermal conductivity are the main controlling parameters affecting safety. Among them, the thermal expansion coefficient is the most sensitive. For every 10% reduction in the thermal expansion coefficient, the safety factor can be increased by 12% to 15%. It is recommended that casing materials with a steel grade of Q125 or higher, a coefficient of thermal expansion ≤ 11.5×10^-6 ℃^-1, and a thermal conductivity ≥ 45 W/(m·K) be selected, and that the heater eccentricity be controlled to ≤ 20 mm with a heating rate of < 10 ℃/d.