The generation of mantle melts in response to decompression by glacial unloading has been linked to enhanced volcanic activity and volatile release in Iceland and in global eruptive records. However, it is unclear whether this process is also important in magmatically-active systems that do not show evidence of enhanced eruption rates. For example, the deglaciation of the Yellowstone ice cap did not observably enhance volcanism, yet Yellowstone may still have released large volumes of CO2 to the surface due to the crystallization of melts at depth. Here we develop models to simulate mantle melt production and volatile release associated with the deglaciation of Yellowstone and Iceland. In agreement with previous work, we find mantle melt production in Iceland is enhanced 33-fold during deglaciation, generating an additional 3728 km3 of melt and releasing an additional 31–51 Gt of CO2. Beneath Yellowstone, we find mantle melt production is comparably enhanced 19-fold during deglaciation, generating an additional 815 km3 of melt, though thicker lithosphere may prevent the transport of this melt to the surface. These melts segregate an additional 135–230 Gt of CO2 from the mantle, representing a ~23–39% increase of the global volcanic CO2 flux (if degassed during deglaciation). Our results suggest deglaciation-enhanced mantle melting is important in continental settings with partially molten mantle (potentially Greenland and West Antarctica) and may result in positive feedbacks between deglaciation and climate warming.