The feedback between atmospheric CO<sub>2</sub> concentrations and silicate weathering is one of the key controls on the long term climate of the Earth. The potential silicate weathering flux (as a function of conditions such as temperature, runoff, and lithology), or "weatherability", is strongly affected by continental configuration, and thus the position of continental landmasses can have substantial impacts on CO<sub>2</sub> drawdown rates. Here, we investigate the potential impact of palaeogeograpical changes on steady-state CO<sub>2</sub> concentrations during the Cretaceous-Eocene period (145–34 Ma) using a coupled global climate and biogeochemical model, GEOCLIM, with higher resolution climate inputs from the HadCM3L General Circulation Model (GCM).</p> <p>We find that palaeogeograpical changes strongly impact CO<sub>2</sub> concentrations by determining the area of landmasses in humid zones and affecting the transport of moisture, that runoff is a strong control on weatherability, and that changes in weatherability could explain long term trends in CO<sub>2</sub> concentrations. As Pangaea broke up, evaporation from the ocean increased and improved moisture transport to the continental interiors, increasing runoff rates and weathering fluxes, resulting in lower steady-state CO<sub>2</sub> concentrations. Into the Cenozoic however, global weatherability appears to "switch" regimes. In the Cenozoic, weatherability appears to be determined by increases in tropical land area, allowing for greater weathering in the tropics.</p> <p>Our modelled CO<sub>2</sub> concentrations show some strong similarities with estimates derived from proxy sources. Crucially, we find that even relatively localised changes in weatherability can have global impacts, highlighting the importance of so-called weathering "hot-spots" for global climate. Our work also highlights the importance of a relatively high-resolution and complexity forcing GCM in order to capture these hot-spots.