Located at the intersection of the Tethys and Pacific Rim metallogenic belts, the Laojunshan polymetallic metallogenic province in SE Yunnan Province hosts many large-scale W–Sn and Sn–Zn polymetallic deposits. The newly discovered Caiyuanzi medium-sized Pb–Zn deposit is located in the northern part of this province and has eight sulfide ore bodies. All the ore bodies occur in the siliceous rocks of the Lower Devonian Pojiao Formation (D₁p). The ore bodies are conformable with stratigraphy and controlled by a lithologic horizon. The sulfide ores have banded or laminated structures. The ore minerals are mainly pyrite, chalcopyrite, sphalerite, and galena. In this study, in situ sulfur and lead isotopes were used to constrain the origin of the Caiyuanzi Pb–Zn deposit. The results show that the in situ δ³⁴S values of pyrite, chalcopyrite, and sphalerite range from 0.1‰ to 6.0‰, with an average of 4.7‰. This δ³⁴S signature reflects the mixing between magmatic-derived and reduced seawater sulfate sulfur. The in situ Pb isotopes characteristics of pyrite, galena, and sphalerite suggest that the sulfur and lead of ore minerals come from the upper crust. Integrating the data obtained from the studies including regional geology, ore geology, and S–Pb isotope geochemistry, we proposed that the Caiyuanzi Pb–Zn deposit is a hydrothermal deposit formed by sedimentary exhalative and magmatic hydrothermal superimposition.