In this study, the effects of prolonged temperature variations on the structural integrity of a historic single-span stone arch bridge were examined using experimental and three-dimensional (3D) analyses. Each stone element of the bridge was independently modeled, and the Burger-creep material model was employed for both the stone elements and the foundation. During the construction of this bridge, Khorasan mortar was utilized to join the stone elements, allowing them to function as a cohesive unit over an extended period without separating. Consequently, Khorasan mortar was applied between the stone elements in this research, and the specific stiffness parameters (ks and kn) at the interface between the Khorasan mortar and the stone elements were computed based on the mechanical properties of the stones and Khorasan mortar. The mechanical properties of Khorasan mortar and stone elements were obtained from experiments. The thermal analysis results revealed distinct thermal stress patterns within the bridge for each month. Higher principal stress values in the arch material of the bridge were observed during December, January, and February in comparison with other months. Additionally, the yearly thermal performance of the bridge was evaluated over 844 years, revealing substantial variations in thermal failures after a certain number of years. Moreover, earthquake analyses were conducted for the bridge, taking into account the monthly thermal analysis outcomes. The study considered the 2023 Kahramanmaras earthquakes (7.7 Mw and 7.6 Mw) for the seismic analyses, and the results demonstrated that temperature fluctuations significantly influence the seismic response of the bridge.