The balance between the subduction of carbonate mineral-bearing rocks into Earth’s mantle and the return of CO2 to the atmosphere by volcanic and metamorphic degassing1, 2, 3, 4 is critical to the carbon cycle. Carbon is thought to be released from subducted rocks mostly by simple devolatilization reactions5, 6, 7. However, these reactions will also retain large amounts of carbon within the subducting slab and have difficulty in accounting for the mass of CO2 emitted from volcanic arcs. Carbon release may therefore occur via fluid-induced dissolution of calcium carbonate8, 9, 10. Here we use carbonate δ18O and δ13C systematics, combined with analyses of rock and fluid inclusion mineralogy and geochemistry, to investigate the alteration of the exhumed Eocene Cycladic subduction complex on the Syros and Tinos islands, Greece. We find that in marble rocks adjacent to two fluid conduits that were active during subduction, the abundance of calcium carbonate drastically decreases approaching the conduits, whereas silicate minerals increase. Up to 60–90% of the CO2 was released from the rocks—far greater than expected via simple devolatilization reactions. The δ18O of the carbonate minerals is 5–10 lighter than is typical for metamorphosed carbonate rocks, implying that isotopically light oxygen was transported by fluid infiltration from the surroundings. We suggest that fluid-mediated carbonate mineral removal, accompanied by silicate mineral precipitation, provides a mechanism for the release of enormous amounts of CO2 from subduction zones.