<p>Mixed sulfide-oxide zinc ore (MSOZO) is characterized by a low zinc grade, high oxidation rate, and high slime content; consequently, it is difficult to efficiently recover zinc from MSOZO via a single mineral processing method. To address this, a novel method combining flotation and ammonia leaching is proposed for efficient zinc recovery from MSOZO. Results indicated that 91.87% of the zinc sulfides present in MSOZO were enriched into zinc sulfide concentrates with a zinc grade of 26.11% via froth flotation, while 96.54% of zinc was effectively leached from the flotation tailings using NH₃–(NH₄)₂SO₄. The zinc grade in the ultimate tailings decreased to 0.21%, and the comprehensive zinc recovery rate reached 97.64%. The cyclic leaching results showed that zinc leaching reached dynamic equilibrium after nine cycles, with a zinc concentration of 26.08 g/L and a leaching efficiency of 65.34%. Subsequently, more than 99% of Zn²⁺ in the circulating leachate was converted into ZnS precipitates when using (NH₄)₂S as a precipitant. Mechanistically, zinc in the flotation tailings was mainly leached as stable Zn(NH₃)₄²⁺ complexes, and the leaching process was controlled by internal diffusion with an activation energy of 11.37 kJ/mol. Thus, this study provides an efficient approach for zinc recovery from MSOZO.</p>