Quantifying how C fluxes will change in the future is a complex task for models because of the coupling between climate, hydrology, and biogeochemical reactions. Here we investigate how pedogenesis of the Peoria loess, which has been weathering for the last 13 kyr, will respond over the next 100 yr of climate change. Using a cascade of numerical models for climate (ARPEGE), vegetation (CARAIB) and weathering (WITCH), we explore the effect of an increase in CO2 of 315 ppmv (1950) to 700 ppmv (2100 projection). The increasing CO2 results in an increase in temperature along the entire transect. In contrast, drainage increases slightly for a focus pedon in the south but decreases strongly in the north. These two variables largely determine the behavior of weathering. In addition, although CO2 production rate increases in the soils in response to global warming, the rate of diffusion back to the atmosphere also increases, maintaining a roughly constant or even decreasing CO2 concentration in the soil gas phase. Our simulations predict that temperature increasing in the next 100 yr causes the weathering rates of the silicates to increase into the future. In contrast, the weathering rate of dolomite – which consumes most of the CO2 – decreases in both end members (south and north) of the transect due to its retrograde solubility. We thus infer slower rates of advance of the dolomite reaction front into the subsurface, and faster rates of advance of the silicate reaction front. However, additional simulations for 9 pedons located along the north–south transect show that the dolomite weathering advance rate will increase in the central part of the Mississippi Valley, owing to a maximum in the response of vertical drainage to the ongoing climate change. The carbonate reaction front can be likened to a terrestrial lysocline because it represents a depth interval over which carbonate dissolution rates increase drastically. However, in contrast to the lower pH and shallower lysocline expected in the oceans with increasing atmospheric CO2, we predict a deeper lysocline in future soils. Furthermore, in the central Mississippi Valley, soil lysocline deepening accelerates but in the south and north the deepening rate slows. This result illustrates the complex behavior of carbonate weathering facing short term global climate change. Predicting the global response of terrestrial weathering to increased atmospheric CO2 and temperature in the future will mostly depend upon our ability to make precise assessments of which areas of the globe increase or decrease in precipitation and soil drainage.