Al-Mg-Si series alloys fabricated by high pressure die casting (HPDC) have a broad application prospect in the production of large-scale and thin-walled die-castings. However, the die-cast Al-Mg-Si series alloys usually exhibit obvious microstructural heterogeneity. This study investigated the microstructural heterogeneity of the die-cast Al-7 Mg-3Si alloy along the thickness direction, and the corresponding formation mechanism was verified. In this study, the die-cast sample can be divided into four distinct regions (R1 ∼ R4) from the surface to the center in turn according to the area fraction of the primary α-Al. Two aspects were considered to be the main reasons for the formation of microstructural heterogeneity. On the one hand, the externally solidified crystals (ESCs) preferentially formed in the shot sleeve and aggregated in the casting center. On the other hand, the cooling rates were quite different in each region, leading to different solidification behaviors. Based on the combination of the microstructural observation and calculated cooling rates, a physical model has been proposed to describe the formation mechanism of the microstructural heterogeneity. The heterogeneous microstructure of the die-cast sample resulted in the inhomogeneity of mechanical properties along the thickness direction. The R2 exhibited the highest micro-hardness than the other regions because of its highest amount of eutectics. Moreover, the casting surface with fine grains (R1) is conducive to improving the EL, whereas the center (R4) showed the lowest tensile properties due to the existence of ESCs and porosity band.