The Eastern Mediterranean resides on the border between the temperate and semi-arid and arid climate zones, and is thus influenced by both mid-latitude and sub-tropical weather systems. Precipitation and extreme weather in this region are mainly associated with either Cyprus Lows or the “wet” Red Sea Troughs. Current regional climate projections indicate that the region may become warmer and drier in future decades. Here, we analyze the influence of enhanced greenhouse gas forcing on the climatological properties of the ‘wet’ and ‘dry’ Red Sea Trough (WRST & DRST, respectively). With this aim, a regional synoptic classification and a downscaling algorithm based on past analogs are applied to eighteen rain stations over the main ground water basins in Israel. The algorithms are applied to the NCEP/NCAR reanalysis data for 1986–2005 and to eight CMIP5 model simulations for the historical (1986–2005) and end of the century (2081–2100) climate conditions according to the RCP8.5 scenario. For the historical period, the CMIP5 models are largely able to represent the characteristics of the Red Sea Trough. Based on the multi-model mean, significant changes are found for WRST and DRST for the late XXI Century. ... mehrFirst, an increase in the meridional pressure gradient is found for both the WRST and the DRST, implying stronger horizontal winds. Furthermore, a significant decrease in the occurrence of the WRST (− 20%) and a significant increase in the frequency of the DRST (+ 19%) are identified. Accordingly, the persistence of the WRST decreases (− 9%), while for DRST increases (+ 9%). The decline in the frequency of WRST occurs primarily in the transition seasons, while the increase for DRST is found throughout the wet season. In total, the daily rainfall associated with the WRST system is projected to significantly decline (− 37%) by the end of the XXI century. These results document the projected changes in a dominant synoptic system in this area, which can facilitate a better estimation of the arising challenges, e.g., related to shortage of water resources and associated political unrest, reduced agricultural potential, and increased air pollution and forest fires. Such a pathway can ultimately foster novel mitigation strategies for water resources management and regional climate change adaptation.