The Saibo skarn–porphyry deposit, located in West Tianshan, NW China, is a large copper deposit discovered recently; however, information regarding the differences and connections between skarn and porphyry mineralization remains limited. Thus, this study aimed to investigate fluid inclusions (FIs), H–O–C–S–Pb isotopes, and U–Pb, and Re–Os geochronology to unravel the origin and evolution of the entire hydrothermal system. Skarn mineralization occurs as stratiform and lenticular in the contact zone between the granodiorite porphyry and Kusongmuqieke Group limestone. We identified four mineralization stages: prograde skarn stage (IS), retrograde skarn stage (IIS), quartz–pyrrhotite–chalcopyrite stage (IIIS), and calcite–quartz–pyrite stage (IVS), and four types of FIs: CH4-rich (C-type), halite-bearing (S-type), vapor-rich (V-type), and liquid-rich (L-type) FIs. The homogenization temperatures (Th) of FIs from stages IS, IIIS, and IVS were 366–419, 271–315, and 174–235 °C, respectively, with salinities of 1.7–46.0, 2.2–9.6, and 4.5–7.7 wt% NaCl eqv., respectively. Porphyry mineralization occurs as veinlet-disseminated ores in the granodiorite porphyry. We identified three mineralization stages: quartz–molybdenite–pyrite stage (IP), quartz–chalcopyrite–pyrite stage (IIP), and calcite–quartz–galena stage (IIIP). Unlike skarn mineralization, only the S-, V-, and L-type FIs were identified, with Th of 332–379, 263–315, and 169–233 °C from stages IP, IIP, and IIIP, respectively, and salinities of 1.9–42.3, 2.2–9.6, and 4.2–6.9 wt% NaCl eqv., respectively. The H–O isotope data indicate that the ore-forming fluids were initially derived from magmatic water and gradually diluted by meteoric water during fluid migration. According to C isotope data and the presence of C-type FIs, fluids from skarn mineralization contained more organic carbon than those from porphyry mineralization. The S–Pb isotope data of sulfides suggest that ore-forming materials are derived from both granodiorite porphyry and the Kusongmuqieke Group, although the latter contributed more to skarn mineralization. Pyrites from porphyry mineralization yielded a Re–Os isochron age of 376.0 ± 7.9 Ma, which was slightly younger than the chalcopyrite Re–Os ages of skarn mineralization (>379 Ma). The granodiorite porphyry, which is considered the ore-causative intrusion, yielded a U–Pb age of 380.8 ± 1.8 Ma. Our results indicate that two styles of mineralization were formed successively at different spatial locations during the emplacement of the granodiorite porphyry in a southward subduction setting of the North Tianshan Ocean. The proposed metallogenic model provides a better understanding of the Saibo skarn–porphyry metallogenic system and is expected to assist in the exploration of similar deposits in the West Tianshan orogenic belt.