Cu and Fe skarns are two economically important types of skarn deposit worldwide, but the critical factors controlling the difference in metal associations remain enigmatic. The Edong ore district, China, presents an excellent opportunity to study the differences between Cu–Fe and Fe skarn deposits. We have measured He–Ar isotopes trapped in fluid released by crushing pyrite and chalcopyrite from four well known Cu–Fe and Fe deposits in the Edong district, Eastern China, with the aim of constraining their different fluid source and then discussing the factors controlling their variations between Cu–Fe and Fe skarns.He–Ar isotopic compositions are markedly different between the Cu–Fe and Fe skarn deposits in the Edong district. 3He/4He ratios in the Cu–Fe deposits are 0.75–1.87Ra and 40Ar/36Ar ratios are 300–472. By contrast, He–Ar isotopic compositions in minerals from the Fe deposits have lower 3He/4He and 40Ar/36Ar ratios of 0.08–0.93Ra and 299–361, respectively. These results suggest that noble gas of the Cu–Fe and Fe skarn deposits in the Edong district formed by variable degrees of mixing between a magmatic fluid containing a mantle component, and modified air–saturated water (MASW). Importantly, He–Ar isotope data provide compelling evidence that contrasting fluid sources were involved in the formation of the Cu–Fe and Fe deposits, i.e., mineralizing fluids of the Cu–Fe deposits could have a greater contribution from mantle component, and little involvement of MASW than those of the Fe deposits in the Edong district. This conclusion is consistent with obvious differences in the nature of the intrusions related to mineralization, as well as sulfur isotopic compositions of sulfides in the Cu–Fe and Fe deposits. It is most likely that different proportion of mantle-derived noble gases play an essential role in controlling differences between the Cu–Fe and Fe skarn deposits.