A comprehensive study was carried out to investigate the effects of Fe addition (0–0.9 wt.%) on the microstructure evolution and mechanical properties of Ti-6Al-4V alloys. The results indicate that Fe addition has a significant refinement effect on the microstructure of titanium alloys; specifically, 0.9 wt.% Fe addition can lead to a 47.37% decrease in the width of lamellar α. The modulus also decreases by 18.89% with the increase in the Fe content, being 91.40 GPa in Ti-6Al-4V-0.9Fe. And the microhardness and wear resistance are improved due to Fe addition. In addition, the constitutive equation of the Fe content and the elastic compliance coefficient were calculated, which can better describe the relationship between Fe addition and the elastic–plastic properties of titanium alloys. The slip systems’ activity during the deformation process was also discussed using the Schmid factor. It shows that Fe addition is beneficial for the activity of prismatic and pyramidal slip systems, especially in the {10 1&#xAF;" role="presentation"> 1̲ 1 ¯ 0} <11 2&#xAF;" role="presentation"> 2̲ 2 ¯ 0>, {10 1&#xAF;" role="presentation"> 1̲ 1 ¯ 1} <11 2&#xAF;" role="presentation"> 2̲ 2 ¯ 3>, and {11 2&#xAF;" role="presentation"> 2̲ 2 ¯ 2} <11 2&#xAF;" role="presentation"> 2̲ 2 ¯ 3> slip systems. Abstract A comprehensive study was carried out to investigate the effects of Fe addition (0–0.9 wt.%) on the microstructure evolution and mechanical properties of Ti-6Al-4V alloys. The results indicate that Fe addition has a significant refinement effect on the microstructure of titanium alloys; specifically, 0.9 wt.% Fe addition can lead to a 47.37% decrease in the width of lamellar α. The modulus also decreases by 18.89% with the increase in the Fe content, being 91.40 GPa in Ti-6Al-4V-0.9Fe. And the microhardness and wear resistance are improved due to Fe addition. In addition, the constitutive equation of the Fe content and the elastic compliance coefficient were calculated, which can better describe the relationship between Fe addition and the elastic–plastic properties of titanium alloys. The slip systems’ activity during the deformation process was also discussed using the Schmid factor. It shows that Fe addition is beneficial for the activity of prismatic and pyramidal slip systems, especially in the {10 1&#xAF;" role="presentation"> 1̲ 1 ¯ 0} <11 2&#xAF;" role="presentation"> 2̲ 2 ¯ 0>, {10 1&#xAF;" role="presentation"> 1̲ 1 ¯ 1} <11 2&#xAF;" role="presentation"> 2̲ 2 ¯ 3>, and {11 2&#xAF;" role="presentation"> 2̲ 2 ¯ 2} <11 2&#xAF;" role="presentation"> 2̲ 2 ¯ 3> slip systems. Keywords: titanium alloys; fe addition; nanoindentation; microstructure refinement; slip system activity