The Eastern Mediterranean Transient (EMT) occurred in the Aegean Sea from 1988 to 1995 and is the most significant intermediate-to-deep Mediterranean overturning perturbation reported by instrumental records. The EMT was likely caused by accumulation of high salinity waters in the Levantine and enhanced heat loss in the Aegean Sea, coupled with surface water freshening in the Sicily Channel. It is still unknown whether similar transients occurred in the past and, if so, what their forcing processes were. In this study, sediments from the Sicily Channel document surface water freshening (SCFR) at 1910 ± 12, 1812 ± 18, 1725 ± 25 and 1580 ± 30 CE. A regional ocean hindcast links SCFR to enhanced deep-water production and in turn to strengthened Mediterranean thermohaline circulation. Independent evidence collected in the Aegean Sea supports this reconstruction, showing that enhanced bottom water ventilation in the Eastern Mediterranean was associated with each SCFR event. Comparison between the records and multi-decadal atmospheric circulation patterns and climatic external forcings indicates that Mediterranean circulation destabilisation occurs during positive North Atlantic Oscillation (NAO) and negative Atlantic Multidecadal Oscillation (AMO) phases, reduced solar activity and strong tropical volcanic eruptions. They may have recurrently produced favourable deep-water formation conditions, both increasing salinity and reducing temperature on multi-decadal time scales.