The major factors especially the roles of the magma evolution controlling the Zn/Cu mineralization in skarn deposits are still controversial. Yaojialing is a large-sized skarn Zn polymetallic deposit (1.74 Mt Zn at 3.6 %, 30.4 t Au at 4.2 g/t and 24.8 t Cu at 0.83 %) located in the Tongling district of the Middle–Lower Yangtze belt (MLYB), both the proximal and distal areas of the deposit exhibit high Zn/Cu mineralization. The intrusions in Yaojialing primarily consist of quartz monzonite porphyry (QMP) and granodiorite porphyry (GDP), and the QMP is related to skarn mineralization. Both the QMP and GDP display relatively high (87Sr/86Sr)i values (0.707907 to 0.709390), low εNd(t) values (−9.05 to −8.17) and negative εHf(t) values (−8.51 to −11.72), suggesting that they originated from a mixed source of enriched mantle and lower crust. Both the QMP and GDP contain type I and type II amphiboles, while type III amphibole exists only in QMP. Type I amphibole is acicular crystals shape, type II amphibole is euhedral in shape and relatively large in size (0.6–2.0 mm), while type III amphibole crystallized around the margin of type II amphibole. The type I amphibole from QMP and GDP show similar calculated temperatures (948–1010 ℃), pressures (2.9–6.5 kbar, corresponding depths at 11.0 to 24.4 km), fO2 (ΔFMQ = 0.2–1.9) and H2O content (4.2–6.8 wt%). Type II amphibole crystallized at 815–941 ℃, 1.2–2.9 kbar (corresponding to depth of 4.6–11.1 km), ΔFMQ = 0.7–2.1, and 4.4–5.7 wt% H2O. Type III amphibole have a lower temperature (679–795 ℃), pressure (<0.5 kbar) and water content (2.5–4.3 wt%) but higher fO2 value (ΔFMQ = 3.1–3.8) compared to type I and type II amphiboles. Reverse zoning of plagioclase and higher Mg# (74 to 89) of type III amphibole in QMP are resulted from injection of mafic magma at shallow depths, which provide sufficient metal and favorable conditions for the formation of QMP parental magma. Modeling of magma H2O solubility indicates that QMP begins to exsolve fluid at depth of 6.2–11.1 km. Initial low oxygen fugacity and ore-forming element differential release during fluid exsolution process resulted in the high Zn/Cu mineralization at Yaojialing.