Pb2+ ions and water glass are commonly used as the activator and depressant, respectively, in the flotation separation of scheelite from calcite and fluorite in industry. The interactive effects of Pb2+ ions and water glass are rarely reported. In this paper, the effects of Pb2+ ions on the flotation behavior of scheelite, calcite, and fluorite in the presence of water glass were investigated through single mineral flotation experiments, zeta potential measurements, solution chemistry calculations, and X-ray photoelectron spectroscopy (XPS) tests. The flotation results showed that at optimal conditions, Pb2+ ions could activate scheelite flotation and enhance the depression effects of water glass on the calcite and fluorite flotation compared with water glass alone. Solution chemistry calculations and zeta potential analysis indicated that after Pb2+ ions adsorption, water glass could strongly adsorb onto the calcite and fluorite surfaces and inhibit the NaOL adsorption, while on the scheelite surface, water glass could hardly adsorb and thus NaOL adsorption continued. XPS results further revealed that Pb2+ ions combined with WO bond to form the W-O-Pb2+ structure on the scheelite surface which could be the active sites for NaOL adsorption, while on the calcite and fluorite surfaces, the Pb-water glass polymers (polycondensation product of water glass and Pb2+ ions) and water glass combined with CaO bond to depress their flotation. Display omitted •Pb2+ ions could slightly activate scheelite flotation in the presence of water glass.•Pb2+ ions could enhance the depression effects of water glass on calcite and fluorite flotation.•Pb2+ ions combined with W‐O bond to form W-O-Pb2+ structure on scheelite surface, which increased NaOl adsorption.•Pb-water glass and water glass combined with Ca‐O bond on calcite and fluorite surfaces, which impeded NaOl adsorption.