Description: Black shale sediments from the Barremian to Aptian South Atlantic document intense and widespread burial of marine organic carbon during the initial stages of seafloor spreading between Africa and South America. The enhanced sequestration of atmospheric CO2 makes these young ocean basins potential drivers of the Early Cretaceous carbon cycle and climate perturbations. The opening of marine gateways between initially restricted basins and related circulation and ventilation changes are a commonly invoked explanation for the transient formation and disappearance of these regional carbon sinks. However, large uncertainties in paleogeographic reconstructions limit the interpretation of available paleoceanographic data and prevent any robust model-based quantifications of the proposed circulation and carbon burial changes. Here, we present a new approach to assess the principal controls on the Early Cretaceous South Atlantic and Southern Ocean circulation changes under full consideration of the uncertainties in available boundary conditions. Specifically, we use a large ensemble of 36 climate model experiments to simulate the Barremian to Albian progressive opening of the Falkland Plateau and Georgia Basin gateways with different configurations of the proto-Drake Passage, the Walvis Ridge, and atmospheric CO2 concentrations. The experiments are designed to complement available geochemical data across the regions and to test circulation scenarios derived from them. All simulations show increased evaporation and intermediate water formation at subtropical latitudes that drive a meridional overturning circulation whose vertical extent is determined by the sill depth of the Falkland Plateau. Densest water masses formed in the southern Angola Basin and potentially reached the deep Cape Basin as Walvis Ridge Overflow Water. Paleogeographic uncertainties are as important as the lack of precise knowledge of atmospheric CO2 levels for the simulated temperature and salinity spread in large parts of the South Atlantic. Overall temperature uncertainties are up to 15 °C and increase significantly with water depth. The ensemble approach reveals temporal changes in the relative importance of geographic and radiative forcings for the simulated oceanographic conditions and, importantly, nonlinear interactions between them. Progressive northward opening of the highly restricted Angola Basin increased the sensitivity of local overturning and upper ocean stratification to atmospheric CO2 concentrations due to large-scale changes in the hydrological cycle, while the chosen proto-Drake Passage depth is critical for the ocean dynamics and CO2 response in the southern South Atlantic. Finally, the simulated processes are integrated into a recent carbon burial framework to document the principal control of the regional gateway evolution on the progressive shift from the prevailing saline and oxygen-depleted subtropical water masses to the dominance of ventilated high-latitude deep waters.