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The Druze Marsh is a spring-fed wetland in northeast Jordan that dried out completely in the late 1980s. This drying and subsequent drop in the water table permitted study of the marsh stratigraphy and a search for prehistoric occupations. In this paper, we combine detailed sedimentological analysis of eight stratigraphic sections in the bed of the former Druze Marsh to reconstruct the landscapes used by hominins since the Middle Pleistocene. The results show that fluctuation in water availability over the past 350 ka had dramatic impacts on the size and depth of the wetlands. Pleistocene occupations in the Druze Marsh correspond to relatively dry climatic conditions when the wetland was reduced in size, suggesting the Druze Marsh acted as a desert refugium for hominins during adverse climatic conditions. Such refugia have important implications for hominin demography, continuity, and/or extinction in the Syro-Arabian Desert. Moreover, the Druze Marsh is positioned at the north end of the Wadi Sirhan depression that connects the Levantine Corridor to the west and Arabian Peninsula to the southeast. Therefore, during wetter climates, paleolakes and river networks around the Druze Marsh may have provided an additional inland route for hominins dispersing between Africa, Eurasia, and the Arabian Peninsula.