Proxy reconstructions and modeling studies of the glacial-interglacial changes in the global carbon cycle have led to a stimulating debate in the paleoclimate literature about the mechanisms leading to a 90–100 ppmv increase in atmospheric CO₂. In this paper, we used the University of Victoria Earth System Climate Model v. 2.9 to simulate the carbon cycle response to ice sheet retreat and Milankovitch (insolation) forcing from the Last Glacial Maximum (LGM) to the present. In addition, we conducted sensitivity studies to address the contributions of CO₂ radiative forcing, atmospheric carbon content, and weathering rates to climate and carbon cycle changes since 21 kyr BP. The simulations show that ice sheet and orbital changes by themselves do not lead to a notable increase in atmospheric CO₂ over the course of deglaciation. However, with the application of CO₂ radiative forcing and different weathering rates, the simulated atmospheric CO₂ variations ranged over ~ 35 ppmv. Virtually all of the simulated net global vegetation carbon uptake since the LGM is attributable to CO₂ fertilization rather than greater land availability or warmer temperatures. Furthermore, the ‘greening’ from CO₂ fertilization significantly enhances total deglacial warming (by 0.14°C) and contributes to warmer intermediate and deep ocean temperatures during the interglacial period. We also found that CO₂ radiative forcing was the dominant factor allowing for greater outgassing at the ocean surface and an earlier ventilation of deep-ocean DIC. The downwelling of high-alkalinity surface waters stimulated by a stronger, earlier overturning circulation led to greater deep sedimentation (alkalinity removal), which, in turn, permitted CO₂ to continue to increase through much of the simulation period.