There are abundant porphyry/skarn Cu deposits in the Chinese Western Tianshan (NW China). However, the differences between the ore-related and barren granitoids, and the metal enrichment mechanism remain controversial. The Lamasu–Saibo deposit (0.6 Mt Cu @ 0.3–6.3%) is the first large-scale Cu discovery in the Chinese Western Tianshan. The Cu orebodies are mainly hosted in the exoskarn of the Proterozoic Kusongmuqieke Group. Here, we present a geochemical comparison study of the ore-related and barren granitoids in the Lamasu–Saibo deposit. The ore-related granodiorite porphyry and barren granite porphyry have zircon U–Pb (LA–ICPMS) ages of 381 ± 2 Ma and 379 ± 2 Ma, respectively. Chalcopyrite from skarn ore yielded a Re–Os age of 379 ± 14 Ma. Hence, the Lamasu–Saibo deposit is suggested to be the oldest Cu mineralization in the Chinese Western Tianshan. The granodiorite porphyry and granite porphyry have similar LREE enriched and HREE depleted patterns, typical of average continental crust. The I_Sr values are calculated to range from 0.707852 to 0.708105 for granite porphyry, 0.708841 to 0.710817 for granodiorite porphyry, respectively. The ε_Nd(t) values of granite porphyry and granodiorite porphyry range from –4.71 to –4.22 and –4.55 to –3.87, respectively. The granite porphyry has ²⁰⁶Pb/²⁰⁴Pb = 18.522 to 18.798, ²⁰⁷Pb/²⁰⁴Pb = 15.552 to 15.569, and ²⁰⁸Pb/²⁰⁴Pb = 38.472 to 38.639; whilst the granodiorite porphyry has ²⁰⁶Pb/²⁰⁴Pb = 18.598 to 18.960, ²⁰⁷Pb/²⁰⁴Pb = 15.544 to 15.566, and ²⁰⁸Pb/²⁰⁴Pb = 38.130 to 38.306. Whole-rock geochemistry and Sr–Nd–Pb isotopes suggest that these granitoids were derived from partial melting of Proterozoic lower crust, and that the parental magma could be metasomatized by subduction-related sediments. The fertile granodiorite porphyry has relatively higher zircon Ce_N/Ce_N* ratio (34 – 202, avg. 111), Ce⁴⁺/Ce³⁺ ratio (88–374, avg. 221), Ce/Nd ratio (7 – 23, avg. 15), log ƒ_O2 (–16.8 to –13.7, avg. –15.6) and ΔFMQ values (–1.0 to +1.5, avg. 0.3) than those of the barren granite porphyry (zircon Ce_N/Ce_N* ratio: 5 – 54 (avg. 34); Ce⁴⁺/Ce³⁺ ratio: 14–123 (avg. 73); Ce/Nd ratio: 2 – 10 (avg. 6); logƒ_O2 value: –17.4 to –14.5 (avg. –16.3); ΔFMQ value: –3.2 to +0.5 (avg. –1.0). The fertile granodiorite porphyry has higher apatite Cl content (0.25 to 0.62 wt%, avg. 0.38 wt%) and lower F/Cl ratio (2.8 to 9.9, avg. 6.7) than those of the barren granite porphyry (apatite Cl content: 0.08 to 0.24 wt%, avg. 0.15 wt%; F/Cl ratio: 9.3 to 29.4, avg. 16.4). This suggests that the fertile granodioritic magma was “wetter” and higher oxidized. Sulfide S–Pb isotope compositions indicate that the ore-forming materials were derived from the granitoids, whilst He isotopes indicate that the ore fluids were dominantly crustal-derived.