With a focus on the Cu isotope geochemistry of chalcopyrite, this paper analyzed the Cu isotope geochemistry of the Qibaoshan crypto-explosive breccia-type Cu–Au polymetallic ore district in Wulian, Shandong Province, North China Craton (NCC). Combined with the results of the in situ sulfur isotope analysis of sulfides, a certain reference and evidence for the study of the genetic mechanism of the epithermal-porphyry Cu polymetallic metallogenic system were provided. The results of the in situ isotope analysis show that the δ34S values of the main sulfides in the Qibaoshan Cu–Au polymetallic ore district range from −6.81‰ to +3.82‰ and are likely to be attributed to the mixing of the derived mantle with the surrounding sedimentary rock assimilation. The ore-forming mechanism may be related to the progressive cooling and transition of the earliest hydrothermal fluids that were dominated by H2S under relatively reducing conditions, followed by a gradual transition from oxidation to reduction. The Cu isotopic composition of the sulfides in ores (δ65Cu = +0.169‰–+0.357‰) decreases with depth, which is likely caused by the upward transport of heavier Cu isotopes. The upper part of the crypto-explosive breccia pipe in the Qibaoshan area may be relatively more gaseous, resulting in the enrichment of δ65Cu. As the gas phase decreases and the liquid phase increases with depth, the δ65Cu value gradually decreases. This indicates the transition from a low-temperature phyllic alteration to a high-temperature K-feldspar alteration. Large, concealed pluton intrusions or orebodies may be present at a depth of the Qibaoshan area. The heavy δ65Cu characteristic is a potential indicator for tracing the fluid activity of the porphyry system and searching for Cu mines. The results provide a reference for the study of the genetic mechanisms of the epithermal-porphyry Cu polymetallic metallogenic system.