Prograde regional metamorphism drives CO2 from carbonate rock to crustal fluids that ascend and ultimately interact with the atmosphere and oceans. The observed loss of CO2 from metamorphic belts remains problematic, however, because the cooling that accompanies fluid ascent favors reactions that add CO2 to metacarbonate rock by removing CO2 from fluids. A new two-dimensional model of coupled mass transfer, chemical reaction, and heat transport was developed to assess how rock devolatilization proceeds along the upward escape paths of crustal fluids during prograde metamorphism. The model is based on upper greenschist to lower amphibolite facies growth of amphibole in metacarbonate layers and garnet and biotite in intercalated metapelite layers of the Wepawaug Schist, Connecticut (Acadian orogeny). The modeling indicates that during heating, CO2 concentrations were larger in metacarbonate layers than in adjacent metapelite layers because amphibole growth in metacarbonates produced CO2, whereas garnet and biotite growth in metapelites produced H2O. The resulting cross-layer concentration gradients drove H2O into the metacarbonate layers and CO2 out by diffusion and the transverse component of mechanical dispersion. Such cross-layer mass transfer can continually force rock decarbonation while fluids ascend, dominating the effects of cooling, unless fluid fluxes are large and prograde heating rates are small. Consequently, prograde metamorphism of carbonate-bearing sedimentary sequences containing significant amounts of pelitic rock will release CO2 to regionally migrating fluids in a wide range of orogenic settings, regardless of whether flow is in a direction of increasing or decreasing temperature. Regional CO2 release can be driven by outcrop-scale processes of volatile exchange between contrasting lithologies.