The tectonically driven Cenozoic closure of the Tethys Ocean invoked a significant reorganization of oceanic circulation and climate patterns on a global scale. This process culminated between the Mid Oligocene and Late Miocene, although its exact timing has remained so far elusive, as does the subsequent evolution of the proto-Mediterranean, primarily due to a lack of reliable, continuous deep-sea records. Here, we present for the first time the framework of the Oligo-Miocene evolution of the deep Levant Basin, based on the chrono-, chemo- and bio- stratigraphy of two deep boreholes from the Eastern Mediterranean. The results reveal a major pulse in terrigeneous mass accumulation rates (MARs) during 24-21 Ma, reflecting the erosional products of the Red Sea rifting and subsequent uplift that drove the collision between the Arabian and Eurasian plates and the effective closure of the Indian Ocean-Mediterranean Seaway. Subsequently, the proto-Mediterranean experienced an increase in primary productivity that peaked during the Mid-Miocene Climate Optimum. A region-wide hiatus across the Serravallian (13.8-11.6 Ma) and a crash in carbonate MARs during the lower Tortonian reflect a dissolution episode that potentially marks the earliest onset of the global middle to late Miocene carbonate crash.