Hydrogen peroxide (H2O2) has been used as an oxidizing agent in the selective flotation of chalcopyrite and molybdenite. However, this method required relatively high concentration of H2O2 to deliver flotation results (i.e., mineral grades and recoveries) comparable to those obtained by the conventional copper-molybdenum (Cu-Mo) ores flotation using sodium hydrosulfide (NaHS). Therefore, further improvements are needed to reduce the consumption of H2O2 reagent. In this study, ferrous sulfate (FeSO4) was used to enhance the oxidation performance of H2O2 through Fenton-like reactions. Flotation results showed that the consumption of H2O2 reagent could be reduced by the addition of FeSO4 without losing the flotation selectivity. The reason might be caused by increasing of oxidation performance as indicated by the increasing concentration of dissolved oxygen after the addition of FeSO4 into the H2O2 aqueous solution. Surface analysis using X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) images showed that the surface of chalcopyrite was covered by more hydrophilic precipitates after the oxidation treatment using H2O2 aqueous solution with the addition of FeSO4, thus more hydrophilic surface and lower floatability. On the other hand, the surface of molybdenite was slightly oxidized and its surface remained hydrophobic as confirmed from contact angle results. Flotation tests using Cu-Mo bulk concentrate demonstrated that selective flotation might be possible using a mixture of FeSO4 and H2O2 aqueous solution. Moreover, this new method could be used as an alternative to copper depressant in Cu-Mo selective flotation, replacing the NaHS reagent.