A catalytic ozonation–microbial fuel cell and Acidithiobacillus ferrooxidans leaching process was used in treating flotation wastewater to remove chemical oxygen demand (COD) and heavy metals in this study. The results indicated that when adding 1 g/L of manganese/modified activated carbon catalyst and 1.5 g/min ozone flow, the COD could be degraded from 2,043.67 mg/L to 711.4 mg/L. After that, the COD could continue decreasing down to 72.56 mg/L through an air-cathode single chamber microbial fuel cell (SCMFCs), coated with 0.4 mg/cm2 platinum catalyst, after 15 days. Meanwhile, the maximum voltages and the ultimate power density of the SCMFCs reached 378.96 mV and 7,608.35 mW/m2, respectively. For filter residue, when 1.2 g/L Fe3+, 10% (m/v) filter residue, and 10% Acidithiobacillus ferrooxidans were added, the copper leaching rate could reach 92.69% after 7 days if the pH values were adjusted to 1.9. Furthermore, the other heavy metals were also decreased to a level lower than the pollution control standard (Chinese standard GB3838-2002). The leaching parameters in terms of pH, redox potential, and cyclic voltammetry showed that the addition of an appropriate concentration of Fe3+ to the leaching systems was beneficial to copper dissolution.