The Elatsite–Chelopech ore field in the northern part of the Panagyurishte district in Central Bulgaria comprises numerous spatially associated porphyry copper and epithermal gold deposits and prospects. In addition to the mineralization and alteration features, trace elements, lead and sulfur isotope signatures of sulfide minerals from porphyry copper, base metal and gold-base metal deposits/prospects have been studied. LA-ICP-MS analyses of pyrite, arsenopyrite and sulfosalt minerals validate them as major carriers for Au, Ag, Sb, Se and Co. Pyrite from the three types of mineralization has specific geochemical characteristics. Pyrite from the porphyry copper deposits/prospects has generally lower total trace element content compared to pyrite from the epithermal prospects, except for Se, Co and Ni. Pyrite from the base metal and gold-base metal veins is enriched in As, Au, Ag, Sb and Pb. In pyrite from the base metal deposits, Co and Ni have contents comparable to the pyrite from the porphyry copper deposits, while pyrite from the gold-base metal veins shows lower Co and Ni. Arsenopyrite from these deposits shows similar features. Similarly, sphalerite from the gold-base metal veins also has lower Co content compared to sphalerite from the base metal veins but higher In and Cu contents. In addition to the close spatial relationships between the Elatsite and Gorna Kamenitsa porphyry Cu deposits and Negarstitsa-West and Dolna Kamenitsa base metal prospects, as well as similarities in the mineralization and alteration styles, the lead isotopic (206Pb/204Pb = 18.61–18.68, 207Pb/204Pb = 15.64–15.65 for porphyry and 206Pb/204Pb = 18.55–18.67, 207Pb/204Pb = 15.64–15.68 for base metal) and sulfur isotopic (δ34S values of −3 to +1‰ for porphyry and δ34S values of −1.7 to +3.5‰ for base metal) signatures of sulfides support the idea of a genetic link between these two types of deposits. The porphyry and base-metal mineralization result from a common major ore-forming event during the Late Cretaceous, corresponding to deep/higher-temperature and shallower/distal/lower-temperature environments, respectively. In particular, more radiogenic lead (206Pb/204Pb = 18.41–18.47, 207Pb/204Pb = 15.67–15.76) and slightly different sulfur isotopic compositions (δ34S values of +3.5 to +10.6‰) of sulfides from the distal gold-base metal veins of Kordunsko Dere, Svishti Plaz and Shipkite might be a consequence of the interaction of the ore-forming fluids with an external older crustal and isotopically positive S source. Alternatively, a different fluid source/event for the formation of these gold-base metal veins may be suggested.