Copper flotation waste is an industrial by-product material produced from the process of manufacturing copper. The main concern with respect to landfilling of copper flotation waste is the release of elements (e.g., salts and heavy metals) when in contact with water, that is, leaching. Copper flotation waste generally contains a significant amount of Cu together with trace elements of other toxic metals, such as Zn, Co, and Pb. The release of heavy metals into the environment has resulted in a number of environmental problems. The aim of this study is to investigate the leaching characteristics of copper flotation waste by use of the Box-Behnken experimental design approach. In order to obtain the optimized condition of leachability, a second-order model was examined. The best leaching conditions achieved were as follows: pH = 9, stirring time = 5 min, and temperature = 41.5 °C.