High CO2 contents were encountered by some exploration wells in the southern part of the upper Permian Zechstein-2-Carbonate (Ca2) fairway of the Lower Saxony Basin in northwestern Germany. The origin of high CO2 accumulations in this part of the Lower Saxony Basin is controversial. In a combined geochemical and structural study, we aimed to decipher the fluid evolution and trace the origin and migration paths of CO2 in the Ca2 reservoirs of the Lower Saxony Basin. The results of comprehensive analyses of fluid inclusions in fracture-filling minerals hosted by Ca2 and sub-Permian strata prove there were multiple stages of fluid and gas migration in the Lower Saxony Basin. Dry gas generated from upper Carboniferous coals charged the Ca2 reservoirs beginning in the Late Triassic and was partly altered in situ by thermochemical sulfate reduction. However, major amounts of CO2 were supplied by rising overpressured hot hydrothermal fluids in response to tectonic movements during Late Cretaceous inversion of the Lower Saxony Basin. Migration of CO2-rich fluids was recorded by fluid inclusions in minerals from fracture-fill mineralization in Devonian, upper Carboniferous, and Ca2 strata. Compelling fluid inclusion evidence indicates that CO2 released during high temperature metamorphism of deeply buried Devonian platform carbonates ascended with hot hydrothermal fluids through deep reaching faults into some Ca2 reservoirs. Locally, reservoirs that were charged with CO2 during Late Cretaceous basin inversion were significantly diluted by sweet gas that migrated laterally from the Pompeckj block southward into the Ca2 fairway beginning in the Paleogene.