CaF₂, NaF and Na₂SiF₆ were chosen as activating fluxes for laser welding of Ti6Al4V (TC4) alloy. During the welding process, the laser-induced plasma images above the weldment were captured with a high-speed camera. After welding, the weld penetration and the width of the weld were measured and the microstructure was observed by an optical microscope. Then, the morphology of acicular martensite in the weld was studied by EBSD, and the element composition of the weld was determined by energy spectrometer. The hardness and tensile strength of the joints were tested. The results show that the activating fluxes change the surface state of the weldment and compress the laser-induced plasma area, thereby increasing the laser absorptivity and the area of the weld melting zone. Besides, all the activating fluxes can increase the penetration depth and reduce the top weld width of the partial penetration weld, and reduce the top weld width while increase the middle and bottom weld widths of the penetration weld. It is also found that for the welds coated with CaF₂, NaF and without activating fluxes, the β columnar crystals on the upper part of the welds all grow towards the weld surface, while for the welds coated with Na₂SiF₆, the β columnar crystals on the upper part of the welds grow towards the weld center. The activating fluxes have no obvious effect on the growing direction of the β columnar crystals of the lower part of the weld. Na₂SiF₆ can significantly refine the acicular α′ in the β columnar crystals of the upper part of the welds in the laser welding of TC4 alloy. The tensile strength of the welded joint coated with Na₂SiF₆ is increased by 12.5%. Compared with other activating fluxes, Na₂SiF₆ has the most prominent effect on the weld formation and mechanical property of the laser welded TC4 titanium alloy, and thus it can be used as the most preferred activating flux.