Compared to calcareous skarn Au-Cu deposits, magnesian skarn (Mg-skarn) Au-Cu deposits are scarce; hence the early evolution of the ore-fluids to late mineralization for the kinds of deposits has been inadequately investigated. Located at the southern margin of the Bangong-Nujiang metallogenic belt, the Galale Au-Cu deposit contains 32.59 tonnes of gold (average grade 2.04 g/t) and 105,600 tonnes of copper (average grade 0.66 %). The orebodies are hosted in an Mg-skarn with associated minerals, including olivine, pyroxene, garnet, and serpentine, which developed in the contact zone between the granodiorite and dolomite of the Jiega Formation. However, the genetic relationship between the Mg-skarn, granodioritic magma, and Au-Cu mineralization remains unclear. The contribution of early stage ore-forming fluids to late Au-Cu mineralization is still vague. In this study, we present the major and trace element compositions, and U–Pb isotope data for garnets obtained from the Galale deposit. We used the data to define the timing, nature, and evolution of early ore-forming fluid and described the genesis of the deposit. The color, at macro- and micro-scales, and chemical composition of the garnets can be used to divide them into two categories, namely early Al-rich Grt-I type garnets, and late stage Fe-rich Grt-II type garnets. In practice, Grt-I (And29.5∼56.1Gro41.3∼68.0Pra1.6∼2.8) and Grt-II (And96.7∼99.9Gro0∼2.7Pra0.1∼0.7) are grossular-andradite solid solution system garnets. Based on the chondrite-normalized REE patterns, Grt-I can be further divided into two sub-classes: Grt-I-1 domain in the core, enriched in HREEs and U, and Grt-I-2 material in the rim, relatively depleted in HREEs. Grt-II is enriched in LREEs and depleted in HREEs. Eu anomalies are slightly negative for the Grt-I-1 domain, weakly positive for the Grt-I-2 domain, and strongly negative for the Grt-II type garnets. The variations in texture and composition in garnets indicated that the formation of Grt-I garnets occurred during diffusive metasomatism in a relatively closed system, in a moderately oxidized ore-forming fluid setting. The formation of Grt-II occurred in a strongly oxidized setting during advective metasomatism in an open system. The enrichment of REE and U in Grt-I garnets was mainly controlled by a “menzerite” type substitution mechanism, partially explaining the strong positive correlation between Mg and REE concentrations. In the Grt-II type garnets, enrichment may also have been co-controlled by coupling substitution and adsorption. In situ U–Pb dating of garnet shows that Grt-I-1 and Grt-I-2 material has isotopic ages of 92 ± 2 Ma (2σ, MSWD = 0.85) and 91 ± 2 Ma (2σ, MSWD = 0.96), respectively. The results were consistent with the previous ages obtained from the granodiorite and Molybdenite using Re–Os isotopic dating within error. This indicates that magma, skarn alteration, and mineralization were spatially and temporally related. In addition, it indicates that the Galale deposit is a typical Mg-skarn Au-Cu deposit. In the earliest stages of deposit development, ore-forming fluids with a high oxygen fugacity (fO2) have inherited their characteristics from the magma. The crystallization of many magnetites during the oxide stage has decreased oxygen fugacity in the metallogenetic system. This has resulted in a relatively low fO2 fluid for Au-Cu precipitation. The study demonstrates that the ore-fluid fO2 plays a vital role in metal migration, hence Au-Cu mineralization in Mg-skarn deposits.