The eastern Mediterranean Sea lies under the influence of high- and low-latitude climatic systems. The northern part of the basin is affected by Atlantic depressions and continental and polar air masses that promote intermediate and deep-water formation. The southern part is influenced by subtropical conditions and monsoon activity. Monsoon intensification results in enhanced freshwater discharge from the Nile River and other (now dry) systems along the North African margin. This freshwater influx into the Mediterranean Sea reduces surface water buoyancy loss. Disentangling the influences of these diverse climatic forcings is hindered by inherent proxy data limitations and by interactions between the climatic forcings. Here we use a wealth of published and new paleoclimate records across Termination II to understand the impacts of the higher latitude and subtropical/monsoon climate influences on coccolithophore ecology and holococcolith preservation in Aegean Sea sediment core LC21. We then use these findings to interpret coccolith assemblage variations at Ocean Drilling Program Site 967 (located nearby LC21, at the Eratosthenes Seamount) during multiple glacial-interglacial cycles across the Middle Pleistocene (marine isotopic stages 14–9). The LC21 analysis suggests that holococcolith preservation was enhanced during Heinrich Stadial 11 (∼133 ka) and cold spell C26 (∼119 ka). These two events have been previously linked to cold conditions in the North Atlantic and Atlantic Meridional Overturning Circulation weakening. We propose that associated atmospheric perturbations over the Mediterranean Sea promoted deep-water formation, and thus holococcolith preservation. Similarly, in the Middle Pleistocene (MIS 14-9) of Site 967, we observe temporal coincidence between ten episodes of enhanced holococcolith preservation and episodes of Atlantic Meridional Overturning Circulation slowdown. In Site 967, we also identified repeated fluctuations in placoliths and in Florisphaera profunda, which indicate nutricline depth variations. The development of a deep chlorophyll maximum is associated with the North Africa and wet phases, as recently observed using elemental proxy records at Site 967, during the deposition of sapropel layers. A further deep chlorophyll maximum development is identified during MISs 12 and 10, as a result of pycnocline and nutricline shoaling within the lower part of the photic zone due to glacial sea-level lowering and water mass transport reduction at both the Gibraltar and Sicily Straits. Finally, enhanced holococcolith preservation during cold/dry events is clearly correlated to weakened monsoon activity in both Africa and Asia.