Fe and Cu skarn deposits constitute the most important skarn type worldwide, whereas the controlling factors that lead to the difference in metal associations remain not well known. The Fe- and Cu-hosting Tieshan complex in the Edong district provides a good opportunity for comparative study on the genetic differences between Fe and Cu skarn deposits. In this study, integrated studies of geochronology, geochemistry and Sr-Nd-Hf isotope compositions were conducted on the complex. LA-ICP-MS zircon U-Pb dating results show that the Tieshan complex was emplaced in the time interval of 135 ± 3 to 144 ± 1 Ma. Multiphase rocks from the complex can be broadly subdivided into two suites. The Fe-Cu-related suite, which consists of diopside diorite, quartz diorite, quartz diorite porphyrite and porphyritic granodiorite, possesses low SiO₂ (53.5–67.1 wt.%), K₂O (2.44–3.53 wt.%) and Rb (45−83 ppm) contents, but high Sr (1132−2684 ppm), Ba (1073−1656 ppm) contents and negligible Eu anomalies, with very high Sr/Y (>90) ratios, similar to typical high Ba-Sr granitoids. The rock suite has initial ⁸⁷Sr/⁸⁶Sr values of 0.70648 to 0.70737, ε_Nd(t) values of −12.3 to −8.2 and ε_Hf(t) values of −16 to −7, comparable to values of the Early Cretaceous mafic rocks in the Edong district and adjacent areas, indicating that it might be largely derived from an enriched lithospheric mantle source, along with minor involvement of lower-crustal components. By contrast, the Fe-related suite, which is composed of quartz diorite, quartz diorite porphyrite and granodiorite porphyry, is characterized by relatively high SiO₂ (63.0–71.0 wt.%) and K₂O contents (3.36–5.53 wt.%), and a wide range of Sr (158−1135 ppm), Ba (762−1366 ppm) contents and Sr/Y (11–99) ratios. In combination with the presence of abundant inherited zircon grains, the lower ε_Nd(t) (−12.4 to −9.3) and ε_Hf(t) (−25 to −15) values indicate a greater degree of lower-crustal contribution for the Fe-related suite. In addition, the calculated zircon Ce (Ce/Ce* and Ce⁴⁺/Ce³⁺) and Eu (Eu/Eu*) anomalies suggest that the Fe-Cu-related suite has much higher oxygen fugacity (fO₂) than the Fe-related suite. This study highlights fO₂ and fractionation degree of magma as useful indicators for differentiating Fe and Cu skarn mineralization.