For multicomponent Al-based alloys, one of the most valuable approaches of microstructural design is to find a path to maximize the multiple microalloying effects while overcoming their negative counterparts. In this paper, triple Sc-Fe-Si microalloying was performed in an Al–Cu alloy to assemble the co-existence of θ′-Al2Cu and Al3Sc precipitates. Besides, the mutual interactions among triple microalloying elements were utilized to maximize the positive effects on tailoring the dual precipitates, as illustrated in two goals of microstructural design: (i). As to θ′-Al2Cu plates, the multiple Sc-Fe-Si segregation at θ′-Al2Cu/matrix interface was preferentially created in the alloy before creep (as-aged condition). During subsequent high-temperature creep, such interfacial warden will be rapidly reinforced by solute repositioning, as a process of accumulating solutes diffusing from both inner θ′-Al2Cu precipitate and outer matrix to limit the interfacial migration. (ii). For Al3Sc precipitates, the beneficial Si microalloying effect on encouraging the nucleation of Sc-rich entities (precursor of Al3Sc) was successfully acquired during aging, while the detrimental Si effect on accelerating Al3Sc coarsening is generally prohibited by tuning Fe–Si synergy within Al3Sc interior. The establishments of (i) and (ii) enable the satisfactory dispersion as well as the outstanding thermal stability of dual precipitates in the current Al-Cu-Sc-Fe-Si system, leading to a good creep resistance at a high homologous temperature of 0.61Tm ~ 300 °C (where Tm is the melting temperature of the α-Al matrix). Display omitted •Triple Sc-Fe-Si microalloying was exploited in an Al–Cu alloy to co-stabilize θ′-Al2Cu and Al3Sc precipitates during 300oC-creeping.•The Sc-Fe-Si co-segregation pattern at θ′-Al2Cu/matrix interface was produced by tuning solute repositioning to greatly suppressing the coarsening.•The Fe–Si synergy maximizes Si microalloying effect by preserving Si-promoted Sc precipitation while avoiding Si-accelerated Al3Sc coarsening.