The evolution of the Antarctic Ice Sheet during the last climate cycle and the interrelation to global atmospheric and ocean circulation remains controversial and plays an important role for our understanding of ice sheet response to modern global warming. The timing and sequence of deglacial warming is relevant for understanding the variability and sensitivity of the Antarctic Ice Sheet to climatic changes, and the continuing rise of atmospheric greenhouse gas concentrations. The Antarctic Ice Sheet is a pivotal component of the global water budget. Freshwater fluxes from the ice sheet may affect the Antarctic Circumpolar Current (ACC), which is strongly impacted by the westerly wind belt in the Southern Hemisphere (SHWW) and constricted to its narrowest extent in the Drake Passage. The flow of ACC water masses through Drake Passage is, therefore, crucial for advancing our understanding of the Southern Ocean’s role in global meridional overturning circulation and global climate change. In order to address orbital and millennial-scale variability of the Antarctic ice sheet and the ACC, we applied a multi-proxy approach on a sediment core from the central Drake Passage including grain size, iceberg-rafted debris, mineral dust, bulk chemical and mineralogical composition, and physical properties. In combination with already published and new sediment records from the Drake Passage and Scotia Sea, as well as high-resolution data from Antarctic ice cores (WDC, EDML), we now have evidence that during glacial times a more northerly extent of the perennial sea-ice zone decreased ACC current velocities in the central Drake Passage. During deglaciation the SHWW shifted southwards due to a decreasing temperature gradient between subtropical and polar latitudes caused by sea ice and ice sheet decline. This in turn caused Southern Hemisphere warming, a more vigorous ACC, stronger Southern Ocean ventilation, and warm Circumpolar Deep Water (CDW) upwelling on Antarctic shelves resulting in increased ice shelf melting. Stronger upwelling is associated with a rise in atmospheric carbon dioxide to reach a threshold at which full deglaciation could become inevitable.