The timing and nature of ice sheet variations on Greenland over the last ˜5 million years remain largely uncertain. Here, we use a coupled climate-vegetation-ice sheet model to determine the climatic sensitivity of Greenland to combined sets of external forcings and internal feedbacks operating on glacial-interglacial timescales. In particular, we assess the role of atmospheric pCO2, orbital forcing, and vegetation dynamics in modifying thresholds for the onset of glaciation in late Pliocene and Pleistocene. The response of circum-Arctic vegetation to declining levels of pCO2 (from 400 to 200 ppmv) and decreasing summer insolation includes a shift from boreal forest to tundra biomes, with implications for the surface energy balance. The expansion of tundra amplifies summer surface cooling and heat loss from the ground, leading to an expanded summer snow cover over Greenland. Atmospheric and land surface fields respond to forcing most prominently in late spring-summer and are more sensitive at lower Pleistocene-like levels of pCO2. We find cold boreal summer orbits produce favorable conditions for ice sheet growth, however simulated ice sheet extents are highly dependent on both background pCO2 levels and land-surface characteristics. As a result, late Pliocene ice sheet configurations on Greenland differ considerably from late Pleistocene, with smaller ice caps on high elevations of southern and eastern Greenland, even when orbital forcing is favorable for ice sheet growth.