The Mediterranean Sea is a large sea almost completely enclosed by Europe, Africa, and SW Asia. Today, the continuous flow of Atlantic seawater through the Strait of Gibraltar balances the net water loss due to the excess of evaporation over input from rain and rivers and keeps the Mediterranean a marine basin with the water level equal to the global ocean level. In the late Miocene, the input of Atlantic seawater was through shallow gateways in southern Spain and northern Morocco. The exhumation of the Betic and Rif Cordilleras and orbitally-controlled regional climate change contributed to the step-by-step close these marine gateways and transformed the Mediterranean into an inhospitable evaporitic sea, starting at 5.96±0.02 Ma. The environmental and hydrological crisis that followed, known as the Messinian Salinity Crisis, peaked at ~5.55 Ma, when a 1.5-2 km-thick salt layer precipitated on the sea floor, and terminated at ~5.332 Ma, when normal marine conditions were re-established, perhaps as a consequence of catastrophic flooding at Gibraltar. The transitional interval from the giant salina to Mediterranean Sea that resembles what we know today is known as the Lago-Mare phase. Gypsum and brackish water biota from the Central Paratethys (approximately coinciding with the present-day Hungary-Slovenia) are both characteristic of Lago-Mare successions. This sedimentary and paleontological evidence suggest that the Mediterranean, during the Lago-Mare phase, experienced a complex history of inter- and extrabasinal connections, base-level fluctuations and extreme environmental and biological changes. This thesis aims to reconstruct the fiercely debated Mediterranean water level changes and identify the hydrological fluxes responsible for these Lago-Mare environmental and biological turnover events. It focuses on key sections exposed on-land and recovered from deep sea cores along an E-W transect across the Mediterranean with a multi-disciplinary approach that integrates biocyclostratigraphic analyses with high-resolution Sr-isotope ratios. The new data show that the Lago-Mare phase was a far more dynamic period of the Mediterranean history than previously thought. Large areas of the Mediterranean were occupied by an anomalohaline water mass predominantly formed by low-salinity waters from the Eastern Paratethys (i.e. the present-day Black-Caspian seas) and from the larger circum-Mediterranean rivers such as the Nile, the Rhône and currently dried North-African rivers. A small and possibly episodic Atlantic flux was a minor contributor. The regular variability of the Mediterranean’s freshwater budget with the astronomic precession combined with fluctuating Atlantic inflow and negligible outflow resulted in a Mediterranean base level that oscillated dramatically, but consistently below eustatic sea level. These precession-paced fluctuations caused the low-salinity Paratethyan biota to colonize the marginal areas of the Mediterranean at times of high base level and central areas during phases of low base level, gypsum to precipitate only in the deeper basins during the regressive phases and silled regions such as the Adriatic and the North Aegean to exist for long as some of the largest endorheic lakes.