Sphalerite is a common sulfide mineral, and xanthate is usually used as the collector of sphalerite flotation. In order to realize the simultaneous flotation of sphalerite- and zinc-containing oxide ores, in this paper, dodecylamine was used as the collector and sodium sulfide as the regulator to explore the flotation behavior of sphalerite in a sulfuration–amine system through single mineral flotation tests, and several analytical methods, including contact angle measurement, adsorption capacity test, FT-IR, and XPS, were employed to discuss the interaction mechanism of dodecylamine on the surface of sphalerite. The results confirm that dodecylamine had a strong collecting effect on sphalerite throughout almost the entire pH range, and the flotation recovery increased with the increase in pH, reaching 86.81% at pH 12. It was found that the effect of sodium sulfide on the floatability of sphalerite was relatively weak, and a weak activation effect, of about 2% improved recovery, was achieved. The results of the mechanism analysis further show that dodecylamine underwent both physical adsorption and chemical adsorption on the surface of sphalerite, and the physical adsorption was enhanced with the increase in pH. The above findings provide evidence for the simultaneous flotation of zinc-containing sulfide-oxide mixed minerals.