We present geochemical data from gas samples from ∼1200 km of arc in the Central Volcanic Zone of the Andes (CVZA), the volcanic arc with the thickest (∼70 km) continental crust globally. The primary goals of this study are to characterize and understand how magmatic gases interact with hydrothermal systems, assess the origins of the major gas species, and constrain gas emission rates. To this end, we use gas chemistry, isotope compositions of H, O, He, C, and S, and SO₂ fluxes from the CVZA. Gas and isotope ratios (CO₂/S_T, CO₂/CH₄, H₂O/S_T, δ¹³C, δ³⁴S, ³He/⁴He) vary dramatically as magmatic gases are progressively affected by hydrothermal processes, reflecting removal and crustal sequestration of reactive species (e.g., S) and addition of less reactive meteoric and crustal components (e.g., He). The observed variations are similar in magnitude to those expected during the magmatic reactivation of volcanoes with hydrothermal systems. Carbon and sulfur isotope compositions of the highest temperature emissions (97–408 °C) are typical of arc magmatic gases. Helium isotope compositions reach values similar to upper mantle in some volcanic gases indicating that transcustal magma systems are effective conduits for volatiles, even through very thick continental crust. However, He isotopes are highly sensitive to even low degrees of hydrothermal interaction and radiogenic overprinting. Previous work has significantly underestimated volatile fluxes from the CVZA; however, emission rates from this study also appear to be lower than typical arcs, which may be related to crustal thickness.