The Baltic Sea is currently the largest marine hypoxic (O2 < 2 mg L− 1) ‘dead zone’ following excessive nutrient input from anthropogenic activities over the past century. Widespread hypoxia has previously developed in the Baltic Sea during the Holocene Thermal Maximum (HTM; 8–4 ka before present; BP) and the Medieval Climate Anomaly (MCA; 1.4–0.7 ka BP). Here we study the mechanisms that contributed to the onset and termination of this past hypoxia using geochemical and marine palynological data from a sediment record retrieved from the Landsort Deep during IODP Expedition 347 (Site M0063). Dinoflagellate cyst records and TEX86L-based sea surface temperature reconstructions indicate a major increase in salinity and temperature prior to and across the onset of the HTM hypoxic interval, underlining the importance of both temperature and salinity stratification in providing conditions conducive to the onset of hypoxia. Both salinity and temperature decline during the termination of the HTM hypoxic interval. In contrast, we find no evidence for significant changes in surface salinity during the MCA hypoxic interval and both the onset and termination of hypoxia appear to have been primarily driven by changes in temperature. Our results indicate that temperature and salinity changes were key drivers of past hypoxia in the Baltic Sea and imply that ongoing climate change will delay recovery from the modern, nutrient-driven hypoxic event in the Baltic Sea.