Die cast is a promising metal forming process that could potentially replace powder metallurgy for producing high Sc-contained Al-Sc sputtering targets. However, die cast of Al-Sc alloys with Sc contents more than 2 wt.% are not yet investigated. This work optimized the die-casting process parameters of Al-Sc alloys based on the air entrainment ratio and shrinkage porosity through numerical simulation and explored the microstructure and mechanical properties of Al-Sc die castings with Sc contents of 2 wt.%, 5 wt.%, and 10 wt.% by experiments. The results show that the influence weighting of parameters on defects is die temperature > pouring temperature > injection velocity, and the optimum parameter combination is pouring temperature of superheat of 60 ℃, die temperature of 240 ℃, and injection velocity of 3 m/s; The solidification structure of Al-Sc die castings comprised equiaxed grains, deformed and partially fragmented columnar grains, and uniformly distributed Al₃Sc precipitates. An increase of Sc content led to grain refinement and a rise in the size and volume fraction of Al₃Sc precipitates. The elongation and tensile strength of Al-Sc die castings were significantly higher than those of gravity castings, whereas these properties diminished with increasing Sc content.