Mixed oxide/sulfide copper ores represent an important but challenging resource for copper production due to the differing flotation behaviors of oxide and sulfide minerals. Conventional studies have primarily focused on overall copper recovery, often overlooking the distinct responses of each copper type. In this study, the Box-Behnken response surface methodology (RSM) was employed to systematically investigate and optimize the effects of collector (potassium amyl xanthate) dosage (100–150 g/t), pulp pH (10–11), and sodium sulfide dosage (1000–2000 g/t) on the recoveries of oxide copper, sulfide copper, and total copper from a low-grade mixed oxide/sulfide copper ore (0.86% total Cu, 66.83% oxidation ratio). Detailed mineralogical characterization using X-ray diffraction (XRD), scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS), electron probe micro-analyzer (EPMA), and size-by-size analysis revealed that the primary copper minerals are chalcocite, bornite, and malachite, predominantly associated with silicate- and clay-rich gangue. Quadratic predictive models were developed for each response, demonstrating high statistical adequacy as confirmed by residual diagnostics and analysis of variance (ANOVA). Pulp pH exerted the strongest influence, with higher values favoring oxide copper flotation and lower values benefiting sulfide copper recovery. Optimal conditions yielded predicted recoveries of 76.49% for oxide copper (100 g/t collector, pH 11.0, 1000 g/t Na₂S), 99.99% for sulfide copper (100 g/t collector, pH 10.0, 1252 g/t Na₂S), and 81.40% for total copper (100 g/t collector, pH 11.0, 1707 g/t Na₂S). The results highlight the necessity of separate optimization strategies for oxide and sulfide fractions in mixed ores and provide practical predictive tools for improving metallurgical performance. This work contributes to a more precise understanding of sulfidization-flotation dynamics and provides a useful basis and guiding framework for the processing of similar mixed copper ores.