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The Fang'an gold deposit in the Wuhe area, Anhui Province, is located in the area adjacent to the Bengbu Uplift and Wuhe Platform Depression in the southeastern part of North China. This study aimed to determine the deposit's mineralization age and the source of its metallogenic materials and mineralization processes through investigations into its geological characteristics, Rb–Sr isotopes, and S–Pb isotopes. The orebodies of the Fang'an gold deposit in the Neoarchean Xigudui Formation primarily exhibit a vein-type structure. The ore-forming process can be divided into four stages: (i) the quartz stage (Py1); (ii) the quartz–pyrite stage (Py2); (iii) the polymetallic sulfide stage (Py3); and (iv) the carbonate stage. Of these, the main mineralization stage is also the main period in which gold mineralization occurs. In situ sulfur isotope results of pyrite (Py1 to Py3) in the first three mineralization stages, suggesting a contribution of sulfur from crust–mantle magmatic fluids. The δ34S values for Py2 (average 5.51‰) are higher than Py1 (average 4.45‰) and showed that the magmatic fluids mixed with meteoric waters. The δ34S values for Py3 (average 5.18‰) are lower than Py2 (average 5.51‰), revealing that it related fluid immiscibility. The lead isotopic compositions of sulfides within the ores possessed 206Pb/204Pb ratios ranging from 16.759 to 16.93, 207Pb/204Pb ratios ranging from 15.311 to 15.402, and 208Pb/204Pb ratios ranging from 37.158 to 37.548. These lead data were plotted close to the Xigudui Formation, relatively distant from the Mesozoic granites, indicating that the Xigudui Formation was the source of lead for the Late Mesozoic ores of the deposit. Taken together, due to the degassing of mantle-derived magma in the shallow parts of the crust, it can be determined that the sources of ore-forming sulfur and lead were crust–mantle magmatic activities in the Wuhe area. Rb–Sr dating of pyrite from Fang'an gold deposit reveals that the mineralization occurred at 126.89 ± 0.58 Ma. Considering the previous research into the dating of magmatic rocks in the Wuhe area, we propose that the genesis of the Fang'an gold deposit is closely associated with magmatic activities in the area at around 130 Ma. [ABSTRACT FROM AUTHOR]