Continental drift and atmospheric greenhouse gas concentrations have each, in turn, been proposed to explain the evolution of Paleozoic climate from early era ice-free conditions to late era continental-scale glaciation, despite continually increasing solar luminosity. To assess the relative roles of continental configuration and atmospheric pCO2 on the formation of continental-scale ice sheets, we use a coupled ice sheet–climate model to simulate ice sheet initiation at eight different Paleozoic time slices using uniform topography. For each time slice, we simulate the climate at three atmospheric pCO2 levels (560, 840, and 1120 ppm) and both constant (97.5% of modern) and time-appropriate solar luminosity values. Under constant luminosity, our results indicate that continental configurations favor ice sheet initiation in the mid-Paleozoic (400–340 Ma). After accounting for solar brightening, ice sheet initiation is favored in the early Paleozoic (480–370 Ma) simulations. Neither of these results is consistent with geological evidence of continental-scale glaciation. Changes in atmospheric pCO2 can reconcile these differences. Sufficiently high (≥1120 ppm) or low (≤560 ppm) pCO2 overcomes paleogeographic and luminosity predispositions to ice-free or ice age conditions. Based on our simulations and geological evidence of glaciation and atmospheric composition, we conclude that atmospheric pCO2 was the primary control on Paleozoic continental-scale glaciation, while paleogeographic configurations and solar irradiance were of secondary importance.