The eastern Mediterranean is undergoing a long-term increase in net evaporation, which may have preconditioned the profound changes that occurred in its deep-sea ventilation over the past two decades. We test the sensitivity of Aegean convective deep-water formation to forcing in the opposite sense, based on a last interglacial episode of enhanced freshwater injection into the eastern Mediterranean. We find that Aegean subsurface ventilation collapsed completely within 40 ± 20 yr, promoting euxinic conditions hostile to aerobic life that expanded toward the photic layer within 650 ± 250 yr. Similar conditions extended throughout the eastern Mediterranean 300 ± 120 yr later. These findings emphasize the exceptional sensitivity of Aegean deep-water formation to climate forcing, driving large-scale hydrographic adjustments throughout the eastern Mediterranean and beyond.