The formation of Eastern Mediterranean sapropels has periodically occurred during intensification of northern hemisphere monsoon precipitation over North Africa. However, the large-scale response of the Eastern Mediterranean thermohaline circulation during these monsoon-fuelled freshening episodes is poorly constrained. Here, we investigate the formation of the youngest sapropel (S1) along an across-slope transect in the Adriatic Sea. Foraminifera-based oxygen index, redox-sensitive elements and biogeochemical parameters reveal – for the first time – that the Adriatic S1 was synchronous with the deposition of south-eastern Mediterranean S1 beds. Proxies of paleo thermohaline currents indicate that the bottom-hugging North Adriatic Dense Water (NAdDW) suddenly decreased at the sapropel onset simultaneously with the maximum freshening of the Levantine Sea during the African Humid Period. We conclude that the lack of the “salty” Levantine Intermediate Water hampered the preconditioning of the northern Adriatic waters necessary for the NAdDW formation prior to the winter cooling. Consequently, a weak NAdDW limited in turn the Eastern Mediterranean Deep Water (EMDWAdriatic) formation with important consequences for the ventilation of the Ionian basin as well. Our results highlight the importance of the Adriatic for the deep water ventilation and the interdependence among the major eastern Mediterranean water masses whose destabilization exerted first-order control on S1 deposition.