Although the flotation behaviors of iron concentrate and quartz are significantly different, quartz is the primary factor that affects the quality of iron concentrate. The flotation mechanism of quartz in the presence of mixed cationic Ca²⁺/Fe³⁺-co-activated SDS catcher was studied by conducting flotation tests with pure quartz mineral. The solution chemical calculation method, zeta potential calculation method, Fourier transform infrared (FT-IR) spectroscopy technique, X-ray photoelectron spectroscopy (XPS) technique, and other techniques were used to conduct the studies. The results showed that the maximum Ca²⁺/Fe³⁺-based synergistic activation of the flotation recovery process could be achieved in a certain range of pH values when three different activators were added sequentially. Analysis of the zeta potential values revealed that the Ca²⁺/Fe³⁺-activated quartz surface improved the extent of positive electricity generated and enhanced the SDS adsorption ability of the quartz surface. Results obtained using the FT-IR technique revealed that Ca²⁺/Fe³⁺ exerted a synergistic effect, and the adsorption process exploited the single oxygen bond interactions in the monovalent hydroxyl complex Ca(OH)+ and the double oxygen bond interactions in the Fe(OH)3 precipitates. Results obtained using the XPS technique revealed that the synergistic effect exerted by Ca²⁺/Fe³⁺ was significantly stronger than that exerted by Ca²⁺ or Fe³⁺ alone. The stable Fe-based six-membered chelate ring was formed on the surface of quartz when Fe³⁺ was the activator, and the chain-like Ca-based complex was formed when Ca²⁺ was the activator. The adsorption process on the surface of quartz proceeded following chemical as well as physical adsorption pathways. The results revealed that Ca(OH)⁺ and Fe(OH)₃ played prominent roles during the activation of quartz surfaces in the presence of Ca²⁺/Fe³⁺.