• H2O2/Fe3+ as a combined depressant enables efficient chalcopyrite–pyrite separation under low-alkalinity conditions, achieving a copper concentrate with 30.51 wt% chalcopyrite grade and >88% recovery.
• Mechanistic analysis reveals that H2O2 selectively oxidizes pyrite disulfide to sulfate and promotes Fe2+→Fe3+, generating hydrophilic Fe–SO4/Fe–OOH/Fe–OH coatings; Fe3+ hydrolysis products further adsorb to form dense hydrophilic layers.
• Chalcopyrite's stable covalent Cu–S bonds resist oxidation and limit Fe3+ adsorption, preserving SEX collector adsorption at copper-active sites and minimizing depression of chalcopyrite.
• The low-alkalinity H2O2/Fe3+ system offers a sustainable, high-selectivity alternative to lime depressants, mitigating scaling, corrosion, and target-metal recovery losses in industrial Cu–S flotation separation.