The coexistence of numerous Mississippi Valley-type (MVT) Pb–Zn deposits and oil/gas reservoirs in the world suggests a close genetic relationship between mineralization and hydrocarbon accumulation. The Wusihe MVT Pb–Zn deposits are located along the southwestern margin of the Sichuan Basin. Based on the spatiotemporal relation between Pb–Zn deposits and paleo-oil/gas reservoirs, ore material sources, and processes of mineralization and hydrocarbon accumulation, a new genetic relationship between mineralization and hydrocarbon accumulation is suggested for these deposits. The Wusihe Pb–Zn deposits are hosted in the Ediacaran Dengying Formation dolostone, accompanied by a large amount of thermally cracked bitumen in the ore bodies. The Pb–Zn deposits and paleo-oil/gas reservoirs are distributed along the paleokarst interface; they overlap spatially, and the ore body occupies the upper part of the paleo-oil/gas reservoirs. Both the Pb–Zn ore and sphalerite are rich in thermally cracked bitumen, in which µm sized galena and sphalerite may be observed, and the contents of lead and zinc in the bitumen are higher than those required for Pb–Zn mineralization. The paleo-oil/gas reservoirs experienced paleo-oil reservoir formation, paleo-gas reservoir generation, and paleo-gas reservoir destruction. The generation time of the paleo-gas reservoirs is similar to the metallogenic time. The source rocks from the Cambrian Qiongzhusi Formation not only provided oil sources for paleo-oil reservoirs but also provided ore-forming metal elements for mineralization. Liquid oil with abundant ore-forming metals accumulated to form paleo-oil reservoirs with mature organic matter in source rocks. As paleo-oil reservoirs were buried, the oil underwent in situ thermal cracking to form overpressure paleo-gas reservoirs and a large amount of bitumen. Along with the thermal cracking of the oil, the metal elements decoupled from organic matter and H₂S formed by thermochemical sulfate reduction (TSR) and minor decomposition of the organic matter dissolved in oilfield brine to form the ore fluid. The large-scale Pb–Zn mineralization is mainly related to the destruction of the overpressured paleo-gas reservoir; the sudden pressure relief caused the ore fluid around the gas–water interface to migrate upward into the paleo-gas reservoirs and induced extensive metal sulfide precipitation in the ore fluid, resulting in special spatiotemporal associated or paragenetic relations of galena, sphalerite, and bitumen.