Anglesite sulfidization mechanism was systematically investigated using flotation tests, X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FESEM), Raman spectroscopy, and ultraviolet- visible diffuse reflectance spectroscopy (UV-Vis DRS). The activation effect of sodium sulfide on anglesite flotation was demonstrated by the flotation tests; however, sodium sulfide concentration must be properly controlled to avoid excessive sulfide ions causing flotation depression. The results of XPS, Raman, and UV-Vis DRS revealed that PbSO₄ was replaced by PbS during anglesite treatment with a sodium sulfide aqueous solution. FESEM imaging shows the dissolution of PbSO₄ and the precipitation of PbS nanoparticles during sulfidization. Thus, it can be suggested that the reaction of anglesite with a sodium sulfide aqueous solution proceeds via an interface-coupled dissolution–precipitation mechanism: upon contact with a sodium sulfide aqueous solution, anglesite dissolution releases Pb²⁺ and SO₄^2– into the fluid boundary layer, which becomes oversaturated with respect to PbS phase; then the PbS nanoparticles nucleate and grow on the surface of anglesite. The PbS nanoparticles grown on anglesite can improve the floatability of anglesite.