In this paper, the synergistic effects of sodium tripolyphosphate (STPP) and sodium ethylenediamine tetramethylenephosphonate (EDTMPS) for the flotation separation from fluorite and calcite were investigated. Flotation tests conducted at various scales demonstrated that the combined inhibitor of STPP and EDTMPS can significantly enhance the separation efficiency of scheelite from fluorite and calcite. For low-grade scheelite in Luanchuan, the combined inhibitor can improve the WO3 grade of scheelite roughing concentrate without compromising the recovery of scheelite roughing, thereby reducing the burden of the Petrov process. Based on the results from X-ray photoelectron spectroscopy and atomic force microscopy, coupled with other surface analysis, it’s evident that STPP and EDTMPS are more readily adsorbed onto the surfaces of fluorite and calcite due to the unique in electrostatic repulsion and steric resistance.The co-adsorption of STPP and EDTMPS covers a more extensive mineral surface area, enhancing the hydrophilicity of fluorite and calcite surfaces. This, in turn, heightens the resistance of the mineral surfaces to subsequent sodium oleate (NaOL) adsorption. As a result, the floatability difference among the three calcium-bearing minerals is expanded, optimizing the separation efficiency.