The Dead Sea fault (DSF) is one of the most active plate boundaries in the world. Understanding the Quaternary history and sediments of the DSF requires investigation into the Neogene development of this plate boundary. DSF lateral motion preceded significant extension and rift morphology by ~10 Ma. Sediments of the Sedom Formation, dated here between 5.0 ± 0.5 Ma and 6.2−2.1 +inf Ma, yielded extremely low 10Be concentrations and 26Al is absent. These reflect the antiquity of the sediments, deposited in the Sedom Lagoon, which evolved in a subdued landscape and was connected to the Mediterranean Sea. The base of the overlying Amora Formation, deposited in the terminal Amora Lake which developed under increasing relief that promoted escarpment incision, was dated at 3.3−0.8 +0.9 Ma. Burial ages of fluvial sediments within caves (3.4 ± 0.2 Ma and 3.6 ± 0.4 Ma) represent the timing of initial incision. Initial DSF topography coincides with the earliest Red Sea MORB's and the East Anatolian fault initiation. These suggest a change in the relative Arabian–African plate motion. This change introduced the rifting component to the DSF followed by a significant subsidence, margin uplift, and a reorganization of relief and drainage pattern in the region resulting in the topographic framework observed today.