Three novel high-entropy alloys, with Cu as their principal components, were produced and studied. The aim of this study was to evaluate the alloy design using raw materials from the Greek industry and to assess the effect of heat treatments on the microstructure and the mechanical properties of these alloys. More specifically, the following alloys have been casted: 1) Cu61,6Zn28,8Al9,5 wt.% and 2) Cu58,2Zn24Al12,4Ni5,4 wt.%. The thermodynamic design was accomplished by using the CALPHAD method and ThermoCalc software. Phase diagrams were calculated, predicting successfully the number of phases in all samples, particularly in elevated temperatures near the solidus. The casting of the alloys was performed in an induction furnace without a protective atmosphere. The selection of the appropriate temperature and the sequence of raw material addition were based on phase diagrams as well as the melting and boiling points of these elements. Heat treatments were conducted for the alloys to investigate the potential microstructural changes. The holding time inside the induction furnace at 700 C was 8 and 16 hours. The Cu-Zn-Al system remained single-phase in both conditions, while the CuZnAlNi alloy exhibited a primary matrix along with a Cu-Ni-Al intermetallic which developed due to exposure to high temperatures. In order to evaluate the mechanical properties of the as-cast and heat-treated samples, hardness tests were performed at room temperature.