Abstract. Understanding the past climate at regional scale, the impact of natural variability and sensitivity by studying the underlying dynamics and processes, can provide a point of reference for future climate conditions under anthropogenic forcing. The Eastern Mediterranean (EM) and Nile River basin (NR) regions are of particular interest for the study of past climate due to their location under the influence of major atmospheric teleconnections. We developed a high-resolution regional model for paleoclimate applications, COSMO-CLM, by integrating all external forcings and conducted a transient simulation from 500 BCE to 1850 CE. Principal Component Analysis (PCA) was applied for winter/summer precipitation and temperature to validate the model set up and showed very good agreement between simulated and observational/reanalysis data. Further, 400–362 BCE and 1800–1850 CE have been selected for the comparison of the mean climate conditions of the early Roman period (ERP) and pre-industrial times (PI). The comparison of temperature and precipitation suggests comparable mean climatic conditions with spatial differences in terms of variability within the study regions. Over the Eastern Mediterranean (EM), ERP is wetter and warmer in both winter and summer compared to PI, with higher variability in temperature and precipitation in summer than in winter. In the Nile River basin (NR), ERP summers were wetter and more variable compared to PI. The ERP over NR is warmer by approximately 0.5 °C in winter and cooler by 0.5 °C in summer, with low variability in winter and high variability in summer compared to PI. The relevant large-scale circulation of the two periods shows consistent spatial structures with the corresponding precipitation/temperature EOF patterns, albeit with varying amplitudes. The 2500 years transient simulation sheds light to the paleoclimate conditions and relevant atmospheric circulation as well as processes of periods of interest in complex areas with detailed output and comprehensive forcing allowing for better representation of the regional climate variability and change. Comparison of simulated output with proxy records, reconstructions and detailed studies of specific events, e.g., volcanic eruptions, can help to capture the spatiotemporal extent of these events and their impact on climate variability and change, in addition to providing insights into their impact on societal change and human history.