The multiple microalloying influences of Si & Sc on the aging behavior and thermal stability of Al-4Cu-0.5Mg alloy were systematically studied. The result revealed that precipitation evolution of Al-4.0Cu-0.5Mg alloy was closely relevant to the content of Si. Si enhanced formation of the Q′ phases serving as nucleation sites for the θ′-Al 2 Cu phases, resulting in a refined distribution of θ′ phases. Al-4.0Cu-0.5Mg-0.40Si-0.1Sc alloy is a combination of high strength and outstanding heat resistance because of the finer and denser Q' & θ′ as well as the segregational structure of Mg, Si and Sc. Especially, the Sc-segregation at the interfaces of θ'/Al is essential to stabilize the microstructure of θ′ precipitates at high temperatures. The solute segregation of Sc atoms in θ′ phases inhibits their coarsening rate. The high-temperature strength of Al-Cu-Mg-Si-Sc alloy are increased dramatically compared with that of typical heat resistant 2618 aluminum alloy. • The effects of Si & Sc on the aging behavior and thermal stability of AlCuMg alloy were studied. • Si has a significant effect on the precipitation evolution in Al-4.0Cu-0.5Mg alloy. • Al-4.0Cu-0.5Mg-0.40Si-0.1Sc alloy achieves a combination of high strength and heat resistance. • The enhanced thermostability of AlCuMgSiSc alloy is attributed to the multiple microalloying segregation of Mg, Si and Sc.