Abstract: Galena (PbS) and chalcopyrite (CuFeS₂) are sulfide minerals that exhibit good floatability characteristics. Thus, efficiently separating them via common flotation is challenging. Herein, a new method of surface sulfuric acid corrosion in conjunction with flotation separation was proposed, and the efficient separation of galena and chalcopyrite was successfully realized. Contact angle test results showed a substantial decrease in surface contact angle and a selective inhibition of surface floatability for corroded galena. Meanwhile, the contact angle and floatability of corroded chalcopyrite remained almost unaffected. Scanning electron microscope results confirmed that sulfuric acid corrosion led to the formation of a dense oxide layer on the galena surface, whereas the chalcopyrite surface remained unaltered. X-ray photoelectron spectroscopy results showed that the chemical state of S²⁻ on the surface of corroded galena was oxidized to \;\mathrmS\mathrmO_4^2- . A layer of hydrophilic PbSO₄ was formed on the surface, leading to a sharp decrease in galena floatability. Meanwhile, new hydrophobic CuS₂, CuS, and Cu_1−xFe_1−yS_2−z species exhibiting good floatability were generated on the chalcopyrite surface. Finally, theoretical analysis results were further verified by corrosion–flotation separation experiments. The galena–chalcopyrite mixture was completely separated via flotation separation under appropriate corrosion acidity, corrosion temperature, and corrosion time. A novel approach has been outlined in this study, providing potential applications in the efficient separation of refractory copper–lead sulfide ore.