The squeeze casting of an Al-4.5 wt pct Cu alloy was carried out to investigate the conditions for the formation and the prevention of macrosegregation. The effects of the process parameters, applied pressure, die temperature, pouring temperature, delay time, and humidity on the formation of macrosegregation were investigated in correlation with the evolution of macrostructure and shrinkage defects. Two critical applied pressures were defined: one is the critical applied pressure, PSC, under which shrinkage defects form, and the other is the critical applied pressure, PMS, above which macrosegregates form in the squeeze castings. A quantitative diagram describing the optimum process conditions was proposed for obtaining sound squeeze castings. It was found that the pouring temperature, the die temperature, the delay time, and the humidity are closely related to the two critical applied pressures PSC and PMS, in different manners. It was concluded that sound castings without macrosegregation and shrinkage defects can only be obtained when the applied pressure is in the range of PSC<P<PMS.