Galena (PbS) is still hard to separate from chalcopyrite (CuFeS₂) in China, necessitating more effective depressants. This study investigated a combined depressant system using sulfuric acid (H₂SO₄) and starch to selectively depress PbS in a PbS−CuFeS₂ mixture. Single-mineral flotation experiments identified the optimal parameters to depress PbS at pH 3, 6 min reaction time, an H2SO4 to starch ratio of 6:1, and 700 mg/dm³ of H₂SO₄. Under these conditions, PbS recovery has decreased to 9.2%, while CuFeS₂ recovery reached 81.1%, Furthermore, the PbS recovery with this combined depressant was significantly lower than the recovery with 700 mg/dm3 of H₂SO₄ (83.2%) or 116.7 mg/dm³ of starch (32.1%). FTIR results also showed that starch molecules could physically adsorb onto the PbS surface. Furthermore, XPS and SEM-EDS analyses revealed that the interaction between H₂SO₄ and the PbS surface produced oxidative components, i.e., Pb-O and SO₄²⁻. These oxidative species may interact with the OH groups in starch molecules, enhancing the adsorption of starch molecules and thus efficiently producing a hydrophilic PbS surface. This study proposes an effective approach for the depression of PbS using the H₂SO₄ and starch combination. These combined reagents exhibit outstanding industrial potential, owing to their low prices.