This study investigates the flotation separation of chalcopyrite and pyrrhotite within a low-alkalinity environment. Single-mineral flotation tests were conducted alongside X-ray photoelectron spectroscopy (XPS) and Materials Studio simulations to systematically evaluate how calcium hypochlorite (Ca(ClO)2) enhances separation performance and alters interfacial chemical mechanisms. Initial results characterized flotation without a depressant. At a potassium amyl xanthate (PAX) dosage of 150 g/t, chalcopyrite and pyrrhotite exhibited similarly high recoveries of 90.56% and 89.24%, respectively, resulting in poor separation efficiency. Density functional theory (DFT) calculations corroborated this, revealing a marginal 0.09 eV difference in PAX adsorption energies between the chalcopyrite (-1.38 eV) and pyrrhotite (-1.29 eV) surfaces. Introducing Ca(ClO)₂ significantly modified the surface properties of both minerals, widening their disparity. The maximum flotation recovery difference was achieved at 1300 g/t Ca(ClO)₂ and 150 g/t PAX. Optimal conditions enriched the Cu grade to 29.12% at an 85.53% recovery, achieving a 3.83 separation index and an excellent Separation Efficiency (SE) of 72.86%. Following Ca(ClO)₂ interaction, surface analyses revealed strong oxidation on the pyrrhotite surface, converting S^2- and Fe²⁺ to SO₄^2- and Fe³⁺. The subsequent accumulation of hydrophilic Fe(OH)3 and SO42- depressed pyrrhotite flotation by hindering PAX adsorption. Conversely, characteristic PAX functional groups (-CH₃, -CH₂-, C-O-C) remained detectable on chalcopyrite. Oxidation on chalcopyrite generated S⁰/Sn^2- and cleaved Cu–S and Fe–S bonds, creating dangling bonds that provided additional active sites for collector interaction. Ultimately, these distinct surface modifications selectively amplified the hydrophobicity difference, providing a mechanistic foundation for the efficient separation of complex copper-sulfur ores.