The Hongtoushan Cu-Zn volcanogenic massive sulfide (VMS) deposit, located in the Hunbei granite–greenstone terrane of the North China Craton, has undergone a complex, multi-stage metallogenic evolution. The deposit comprises three main types of massive ores: Type-1 ores, characterized by a sulfide matrix enclosing granular quartz and dark mineral aggregates; Type-2 ores, distinguished by large pyrite and pyrrhotite porphyroblasts and a small amount of gangue minerals; and Type-3 ores, mainly distributed in the contact zone between the ore body and gneiss, featuring remobilized chalcopyrite and sphalerite filling the cracks of pyrite. The metallogenic process of the Hongtoushan deposit is divided into three main stages: (1) an early mineralization stage forming Type-1 massive ores; (2) a metamorphic recrystallization stage resulting in Type-2 massive ores with distinct textural features; and (3) a late-stage mineralization event producing Type-3 massive ores enriched in Cu, Zn, and other metals. This study integrates sulfur isotope, trace elements, and fluid inclusion data to constrain the sources of ore-forming materials, fluid evolution and metallogenic processes of the deposit. Sulfur isotope analyses of sulfide samples yield δ34S values ranging from −0.7 to 4.2 (mean: 1.8 ± 1.5, 1σ), suggesting a predominant magmatic sulfur source with possible contributions from Archean seawater. Trace element analyses of pyrite grains from different ore types reveal a depletion of rare earth elements, Cu, and Zn in Type-2 massive ores due to metamorphic recrystallization, and a subsequent re-enrichment of these elements in Type-3 massive ores. Fluid inclusion studies allowed for identifying three types of ore-forming fluids: Type-1 (avg. Th: 222.9; salinity: 6.74 wt.% NaCl eqv.), Type-2 (avg. Th: 185.72; salinity: 16.56 wt.% NaCl eqv.), and Type-3 (avg. Th: 184.81; salinity: 16.22 wt.% NaCl eqv.), representing a complex evolution involving cooling, water–rock interaction and fluid mixing. This multi-disciplinary study reveals the interplay of magmatic, hydrothermal and metamorphic processes in the formation of the Hongtoushan VMS deposit, providing new insights into the fluid evolution and metallogenic mechanisms of similar deposits in ancient granite–greenstone terranes.