A number of significant gold deposits in the Kassan region in west Kyrgyzstan are associated with the Andagul granitic intrusion. These gold deposits share similarities with the class of “intrusion-related gold deposits”, implying that the gold mineralization may be genetically related to the intrusion. In order to evaluate this potential relationship, it is important to study the petrogenesis of the intrusion. This paper examines the sources and physiochemical conditions of magma generation and crystallization of the Andagul intrusion and their implications for gold mineralization, through an integrated study involving zircon geochronology, mineral chemistry, whole-rock chemistry and isotopic geochemistry. The Andagul intrusion consists mainly of granodiorite, which is characterized by metaluminous and median-K calc-alkaline compositions, high LREE and LILE, low HFSE, right-inclined REE pattern with a flat HREE pattern, and insignificant Eu anomalies ((Eu/Eu∗)N = 0.79–0.85). These geochemical characteristics, together with relatively low positive εNd(t) values (+2.1–+4.3), moderately low (87Sr/86Sr)i ratios (0.7049–0.7059), relatively low initial Pb isotopic ratios ((206Pb/204Pb)t = 17.76–18.51, (207Pb/204Pb)t = 15.56–15.62, and (208Pb/204Pb)t = 37.89–38.33), juvenile εHf(t) (+2.29–+4.80) but relatively old model ages (T2DM(Hf) = 1026–1175 Ma, T2DM(Nd) = 728–907 Ma) indicate that the magma was mainly sourced from partial melting of juvenile basaltic lower crust with the involvement of a small proportion (ca. 5%–10%) of Precambrian basement rocks. The high Zr saturation temperatures (807 °C to 825 °C), relatively high Mg# values (43–52) and presence of mafic enclaves, and development of acicular apatite and oscillatory plagioclase and titanite, suggest that the magmatism was related to injection of hot mantle material. The magma generation and intrusion took place during 299–310 Ma based on LA-ICPMS zircon U-Pb dating, suggesting a post-collisional setting. Remelting of sulfide accumulate residual with high Au/Cu ratios in the juvenile lower crust, formed in the pre-collisional plate subduction-related magmatic arc stage, is proposed to account for the Au mineralization in the Kassan region. The high water contents (4.0–5.2 wt% H2O) and weakly oxidized or slightly reduced redox state (ΔFMQ = −0.33 ∼ +0.49) deduced from mineral composition and zircon Ce anomaly are favorable for the transport and enrichment of gold in the magmatic fluids. These geochemical characteristics suggest that the Andagul granodiorite and related granitic rocks in the Kassan region have the potential to provide ore-forming materials and fluids for gold mineralization.