Abstract: Tantalum (Ta) and niobium (Nb) are key strategic metals used in the aerospace, steel, and chemical industries. Columbite‒tantalite is the primary Ta- and Nb-containing mineral. Flotation is an effective and practical approach for preconcentrating columbite‒tantalite. However, the inevitable introduction of Ca, Mg, and other ions from process water and mineral dissolution during beneficiation can significantly affect the flotation performance of columbite‒tantalite. This study systematically investigated the effects of Ca²⁺ and Mg²⁺ on columbite‒tantalite flotation in a sodium oleate (NaOL) system. Flotation experiments revealed that, at pH = 10, the addition of Ca²⁺ and Mg²⁺ markedly suppressed the flotation of columbite–tantalite, reducing the recovery by 94.86% and 92.55%, respectively. Characterization revealed that NaOL forms a hexagonal ring structure with Mn sites on the columbite‒tantalite (100) crystal surface. However, Ca²⁺ and Mg²⁺ ions interfere with the chemical adsorption of NaOL by reacting with it to form oleate precipitates, which subsequently cover the mineral surface. Therefore, excess NaOL did not facilitate the effective flotation of columbite‒tantalite. Furthermore, NaOL, as compared with the columbite‒tantalite surface, tended to interact with Ca²⁺ and Mg²⁺ to deactivate the collector. This paper elucidates the inhibitory effects of Ca²⁺ and Mg²⁺ on the flotation of columbite‒tantalite. Consequently, the selective removal of metal ions, such as Ca²⁺ and Mg²⁺, from the slurry is essential to improve both the flotation efficiency and recovery of columbite‒tantalite, particularly when processing ores with high water hardness or containing easily leachable metal ions.