The mechanical behavior of lead/rubber bearings (LRBs) is strongly influenced by both ambient temperature and hysteretic heating under seismic loading; however, their coupled effects and underlying mechanisms remain insufficiently understood. This study presents a systematic investigation of the thermo-mechanical response of LRBs through combined experimental and numerical approaches. Dynamic cyclic tests were conducted on full-scale LRBs (700 mm in diameter) over a wide range of ambient temperatures, revealing that ambient temperature and hysteretic heating jointly govern the evolution of key mechanical properties, including stiffness, characteristic strength, and energy dissipation capacity. Specifically, decreasing temperature leads to stiffness and strength enhancement, whereas hysteretic heating induced by cyclic plastic deformation of the lead core results in progressive softening and degradation of restoring force. Based on the experimental observations, a modified uniaxial Bouc–Wen constitutive model is developed, incorporating the coupled effects of ambient temperature, hysteretic heating, and large-strain hardening. The proposed model is implemented in a single-degree-of-freedom (SDOF) base-isolated system to evaluate the seismic response under different temperature conditions. The results reveal a competing mechanism between ambient temperature and hysteretic heating: low temperatures tend to increase base shear and reduce displacement, while hysteretic heating produces the opposite effect, with their relative dominance depending on temperature level and ground motion intensity. Neglecting such thermo-mechanical coupling may lead to significant misestimation of structural response, particularly under long-duration strong ground motions. This study provides new insights into the coupled temperature-dependent behavior of LRBs and establishes a robust modeling framework for the seismic analysis and design of isolation systems under complex service conditions.