High-entropy alloys of hexagonal structure commonly revealing high strength but very limited ductility, still remain a challenging task. Advanced strategy is proposed in present work in order to develop high-entropy alloy of chemical composition Al 10 Hf 25 Nb 5 Sc 10 Ti 25 Zr 25 at.%. Crystallographic features and microstructures of as-cast and annealed Al 10 Hf 25 Nb 5 Sc 10 Ti 25 Zr 25 at.% alloy are characterized by X-ray diffraction, scanning and highresolution transmission electron microscopies, whereas differential scanning calorimetry is used to follow temperature-induced phase transformation in the as-cast system. The cast alloy reveals microstructure containing fine orthorhombic needle-like plates within solid-solution of body-centered cubic structure. Such a dual-phase microstructure leads to enhanced combination of high strength and good ductility. The alloy annealed at 1000 • C for 5h acquires tensile strength increased by 38%, yield strength more than ten times higher, and almost 3-fold increased plasticity as compared with the as-cast alloy. Its Vickers hardness becomes higher by 25%. These meaningful changes are associated with temperature-induced transformation of its microstructure, which include diffusion growth of hexagonal plates enriched in Zr, Sc, and Hf within the bcc-type matrix enriched in Nb and Ti. Microstructure reveals twins within the hcp plates which plays a crucial role in plastic deformation and strengthening of the materials. Ab initio calculations based on the density functional theory are employed to investigate stability and mechanical properties of bcc, hcp, and orthorhombic phases of 5-component Al 15 Hf 25 Sc 10 Ti 25 Zr 25 at.% and 6-component Al 10 Hf 25 Nb 5 Sc 10 Ti 25 Zr 25 at.% high entropy alloys. The hcp phases of both systems are energetically preferred at T = 0 K, brittle and have rather high Vickers hardness. The bcc phases of both high-entropy alloys stabilize and become energetically favored above 790 K for Al 15 Hf 25 Sc 10-Ti 25 Zr 25 at.% and 1150 K for Al 10 Hf 25 Nb 5 Sc 10 Ti 25 Zr 25 at.% alloys. Depending on the type of crystallographic structure, the phases enriched in 5 at% of Nb show either reduced or enhanced values of their elastic moduli and Vickers hardness as compared to the Nb-free phases. No transformation from brittle to ductile state and vice versa is observed upon doping the considered phases of Al-Hf-Sc-Ti-Zr system with Nb.