Relics of a thick, widely spread, fluvial sequence of Early Miocene age are scattered throughout southern Israel, eastern Sinai, the Dead Sea Rift Valley and the western margins of the Jordanian Plateau. These relics are mainly preserved in structural lows, karstic systems, and abandoned stream valleys. The paleogeography of this fluvial system was reconstructed based on the relations between the sequence remnants and the main structural and morphological features of the southeastern Levant region.Three sedimentary associations were identified in the Miocene sequence: a lower part dominated by locally derived clastic sediments; a thicker middle part, composed mostly of far-field allochthonous clastic sediments; and an upper part composed of local as well as allochthonous sediments. The two lower parts are regionally distributed whereas the upper part is syn-tectonic and confined to the Dead Sea basin and the Karkom graben in the central Negev. The composition of the far-field allochthonous sediments points to a provenance of Precambrian crystalline rocks of the Arabo-Nubian massif that were exposed along the uplifted shoulders of the Red Sea Rift as the upper drainage basin of the fluvial system. The diverse mammal remains found in this fluvial sequence suggest a complex of savanna, forests and fluvial habitats similar to those of present East Africa, with monsoon-type rains, which were the dominant water source of the rivers.The thickness of the Miocene sequence in the central Negev is at least 1700m, similar to that of the subsurface sequence encountered in the Dead Sea basin. This similarity suggests that both were parts of an extensive subsiding sedimentary basin that developed between the Neo-Tethys and the uplifted margins of the Red Sea.The relations between the reconstructed pre-depositional landscape of southern Israel during the Early Miocene and the overlying fluvial sequence indicate that the entire area was buried under several hundred meters of fluvial sediments, reflecting a subsidence of the northern margins of the African continent (Arabian plate) before its breakup and the splitting of the Sinai–Israel subplate by the Dead Sea Transform.During the early Middle Miocene the subsidence was inversed as the mountainous backbone of Israel was uplifted. The uplift triggered a large scale denudation that removed the thick Early Miocene fluvial sequence from the Negev and transported the eroded sediments northwestward toward the eastern Mediterranean basin. Additional uplift during the late-Middle Miocene was associated with entrenchment of the Be’er Sheva Valley between the Judea Mountains in the north and the Negev Highlands in the south. This valley was flooded by the sea during the Late Miocene.We suggest that the formation of the Early Miocene subsiding basin at the northern edge of the Arabian sub-plate predated the breakup of the Arabian plate by the DST. The inversion of the subsiding regime, which led to the establishment of the Negev Highlands seems to be intimately related to the detachment of the Sinai–Israel sub-plate from the Arabian plate during the Middle Miocene.