The Messinian Salinity Crisis (MSC) forms the most dramatic chapter of Mediterranean history, occurring at the end of the Miocene. Around 5.96 million years ago, the convergence of the African and Eurasian plates following the closure of the Tethys Ocean sealed the shallow seaways near the present-day Spain-Morocco boundary, cutting off water exchange between the Atlantic and the Mediterranean.

Once the connection was severed, evaporation became the Mediterranean's destiny. In the tropical climate, the basin shrank progressively; the accumulated salt, gypsum, and anhydrite deposits reach 3 to 5 kilometres in thickness in some regions. The evaporite beds visible in the rocky outcrops of Italy, Spain, Greece, and Turkey are the stratigraphic signature of this episode. Sicily's Gessoso-Solfifera Formation and Spain's Lorca Basin are among the best-studied examples.

Whether the basin dried completely or merely shallowed dramatically remains debated. Deep borehole data contain erosion surfaces — traces of the Messinian Erosional Surface (MES) — indicating that large rivers incised hundreds of metres into the drying Mediterranean floor. Major rivers including the Nile, Rhône, and Var left submerged canyons that now lie buried beneath the sea floor.

Around 5.33 million years ago, in the event known as the Zanclean Flood, a threshold in southern Spain or northern Morocco was breached or eroded and Atlantic waters began filling this enormous depression. Some modelling suggests the refilling was completed within a few hundred to a few thousand years, with flow rates in the earliest stages potentially reaching thousands of times the combined discharge of all present-day rivers — a flood in the full geological sense of the word.

The regional climatic impact of the MSC was also significant. As the Mediterranean evaporated, North Africa and the Middle East dried further; the overlap of this aridification with Pliocene hominin speciation patterns has led some researchers to seek a connection between the early evolution of human ancestors and Mediterranean geology.