<p>The wide application of additive-manufactured Ti alloys is impeded by coarse columnar grains along the building direction and thus the severe anisotropy of mechanical properties. To address this issue, a novel multi-alloying CoCrMoSi strategy has been developed to produce near-equiaxed grains of a modified Ti6Al4V (TC4) alloy for laser-directed energy deposition (LDED) based on computational thermodynamic and experimental approaches. The results show that the microstructure of the TC4 alloy consists of large columnar β grains and α/α' laths with a high aspect ratio of 5.73, exhibiting a strong anisotropy of tensile properties. In contrast, the TC4-1.5%CoCrMoSi alloy is characterized by mixed columnar-equiaxed β grains and near-equiaxed β grains with increased CoCrMoSi additions to 4.5%. Additionally, the α/α' laths are successively refined with the increase of CoCrMoSi content, showing an aspect ratio of smaller than 4.31. However, an excess addition of CoCrMoSi leads to the formation of microvoids. After multi-alloying CoCrMoSi, the number density of twins increases remarkably with a substantially reduced width, because of the increased lattice distortion and dislocation density together with the reduced β → α phase transformation temperature. The anisotropy of the tensile properties can be effectively eliminated by adding 3 wt% CoCrMoSi with an exemplary strength–ductility combination, superior to the LDEDed-modified TC4 alloy in the literature reporting the tensile properties along both horizontal (<i>X</i>) and vertical (<i>Z</i>) directions. The underlaying mechanisms for the evolution of the microstructure and the tensile properties induced by multi-alloying CoCrMoSi were discussed in detail.</p> Graphical abstract <p></p>