We use an asynchronously coupled atmosphere-ocean model to examine the response of the oceanic thermohaline circulation (THC) to increased atmospheric CO2 and lowered topography. In Experiment 3CO2, CO2 was tripled relative to modern with no accompanying reductions in topography. In Experiment LT3CO2, CO2 was also tripled, in combination with lowered topography (LT), with elevation reductions for all major mountain ranges and ice sheets to approximate paleoclimatic conditions prior to recent major uplift and CO2 draw down (before 10 Ma). Although the THC changes from the control simulation by at least 25% in both experiments, the THC weakens with higher CO2 alone but strengthens with higher CO2 and lowered topography. The stronger THC in LT3CO2 is caused by the removal of the Tibetan Plateau and the Greenland Ice Sheet. Lowering these features alters the atmospheric circulation to promote Arctic air flow over the convective North Atlantic, thereby destabilizing the upper ocean.