The Astrakhan Arch region contains one of the largest sub-salt structures of the Pricaspian basin, where perspectives for hydrocarbon generation and accumulation in the Devonian to Carboniferous deposits are considered to be high. The paper addresses the problem of structural and geothermal evolution of the region deformed by salt movements. Initially, we developed a model of the regional structural evolution along a geological profile using the volume-balancing and back-stripping methods and geological constraints on the sedimentation, erosion, and paleo-water depths. Then we developed geothermal models (along the study profile) associated with the regional structural evolution. The models were constrained by the temperatures measured in four deep boreholes along the profile. We show that the present temperatures and heat flux are influenced by the presence of salt diapirs. Since the Early Carboniferous and till Middle Permian times, the temperatures predicted by the models vary significantly due to the regional transgression and the presence of seawater. The temperature of Devonian-Carboniferous carbonates increases since the Late Permian (time of postsalt deposition) and attains its maximum values in the SWpart of the profile. If the model assumptions concerning the constant vertical and zero lateral heat fluxes are valid, we can conclude that hydrocarbons are most likely to be generated in the SW-part of the region for the post-Early Permian time.