The normal and inverse solute macro-segregation are known to occur in Al and other nonferrous alloy castings and have been well studied and documented. However, these phenomena have not been investigated in the high-pressure die-cast Mg-alloys. Consequently, the effects of macro-segregation on the mechanical properties of cast Mg-alloys have not been characterized. The objective of this contribution is to investigate the effects of inverse macro-segregation and porosity on the fatigue behavior of high-pressure die-cast AM60 alloy. It is observed that the inverse macro-segregation of eutectic phase at the cast surfaces adversely affects the fatigue behavior: the fatigue resistance decreases substantially due to the presence of the surface segregation.