The climatic history of the Dead Sea region during the Pliocene and its global connection are observed from climate-sensitive rocks and clay minerals of the Sedom formation. The Sedom formation consists of evaporative halitic rock salt units and calcareous shale units that were deposited in the Dead Sea Basin during the Pliocene. The precipitation of the rock salts took place in the hypersaline sabkha environment of the Sedom Lagoon. The extensive evaporative conditions are related to an extremely dry and warm arid climate at that time. In the arid climate, the influx of meteoric water by the drainage system of the Sedom Lagoon was limited and permitted a large concentration of lagoonal brine as well as a small rate of detritus transportation to the lagoon. Accessory sepiolite found in the rock salt appears to be neoformed from brine enriched with Mg and poor in Al under the extreme salinity condition. The small amounts of Al are in accordance with the small number of detrital minerals in the rock salts. The replacement in the deposition of the rock salt members with the calcareous shale members demonstrates a decrease in the salinity of the brine in the Sedom Basin and an increase in the deposition of detritus. The change in conditions was related to a period of deposition under a more humid climate where the erosion and the transport of detritus by the drainage system to the Sedom Basin was higher, causing the deposition of calcareous shales. Palygorskite found in the calcareous shales appears to be neoformed from brine enriched with Mg and containing Al in conditions of reduced salinity of the Sedom Basin. The larger amounts of Al are in accordance with the abundance of detrital minerals in the calcareous shales. The depositional cycles of the Sedom formation, the cyclic fluctuation of the climatic-hydrologic conditions from an arid to a more humid climate and their correlation with sea-level fluctuations and transgression-regression cycles of the Mediterranean Sea seem to be a response to corresponding global interglacial and glacial periods during the Pliocene.