Ore deposition took place in the Yangtze Valley episodically during the Jurassic and Cretaceous periods, generating approximately 200 polymetallic Cu–Fe–Au, Mo, Zn, Pb, and Ag deposits. We analysed the stable isotopes of sulphur, oxygen, and hydrogen from the Cu–Au deposits and correlated our new data with published stable isotope for associated Yanshanian (Mesozoic) igneous rocks. The latter bears a close relationship to Cu–Au mineralization in the area. Cu–Au deposits in the middle–lower Yangtze Valley can be divided into three types: skarn, porphyry, and volcanic. The S–O–H isotopic values allow constraints to be placed on the conditions of origin of these famous Cu–Au ores and their related igneous rocks. Sulphur from the sulphide ores mostly was derived from a magmatic source; however, a few deposits reflect a sedimentary source of sulphur. Oxygen isotope values in quartz from the Shaxi porphyry Cu–Au deposit and from the Tongling skarn Cu–Au deposits range from 2.6‰ to 12.5‰ and from −1.3‰ to 24.5‰, respectively; these values represent larger variations compared with those from other Cu–Au deposits in this metallogenic belt. Hydrogen versus oxygen isotope plots of the Cu–Au ore-forming fluids demonstrate that the fluids came from different sources: the most important involved the mixing of magmatic and meteoric water; the second most important was strictly magmatic water; and the third most important may have been a mixture of formation water or meteoric water that had reacted with carbonate wall rocks.