The Afro-Arabian dome is a broad (4000 × 1500 km) topographic swell extending from Ethiopia to the Eastern Mediterranean, initiated by Late Eocene epeirogeny associated with the Afar plume and further shaped by Oligo-Miocene rifting of the Red Sea. Here, we evaluate stages in the uplift history of Afro-Arabia by analysing the mineralogical and geochemical properties of Oligocene-Miocene sediments from the Levant Basin of the Eastern Mediterranean. Our findings show that the 3-km-thick siliciclastic section in the basin preserves a unique record of the regional-scale uplift in Afro-Arabia, revealing a three-stage evolution: (1) Oligocene sediments (∼33–25 Ma) exhibit extreme weathering signatures reflecting deep chemical alteration of Neoproterozoic basement rocks of the Arabian-Nubian Shield. These sediments record the erosion of widespread Late Cretaceous-Late Eocene etchplains that blanketed the region and were dismantled during early stages of mantle-driven domal uplift; (2) A major transition occurred in the Late Oligocene-Early Miocene (∼25–20 Ma) when sedimentation rates peaked, sediment weathering intensity declined and recycling intensified, reflecting more vigorous erosion as uplift accelerated along the emerging Red Sea Rift shoulders; (3) Since ∼20 Ma, sediments show reduced weathering intensity, reflecting incision through the residual weathering mantle into fresh basement and marking the development of a rugged, high-relief landscape. Together, this record documents a stepwise transition from a deeply weathered, low-relief surface to a high-relief topography, shaped by the combined effects of regional doming and flexural uplift along the Red Sea Rift margins. It provides independent sedimentary constraints on the timing and style of Oligocene-Miocene uplift of Afro-Arabia.