Reconstructions of Phanerozoic CO2 levels have generally relied on geochemical modeling or proxy data. Because the uncertainty inherent in such reconstructions is large enough to be climatically significant, inverse climate modeling may help to constrain paleo-CO2 estimates. In particular, we test the plausibility of this technique by focusing on the climate from 360 to 260 Ma, a time in which the Siberian landmass was in middle to high latitudes, yet had little or no permanent land ice. Our climate model simulations predict a lower limit for CO2—the value beneath which Siberia acquires “excess” ice. Simulations provide little new information for the period in which Siberia was at a relatively low paleoaltitude (360–340 Ma), but model results imply that paleo-CO2 levels had to be greater than 2–4× modern values to be consistent with an apparently ice-free Siberia in the late Permian. These results for the later period in general agree with soil CO2 proxies and the timing of Gondwanan deglaciation, thus providing support for a significant CO2 increase before the end-Permian boundary event. Our technique may be applicable to other time intervals of unipolar glaciation.