In this study, tribo-corrosion behavior of TC4-Cu coatings with hypoeutectoid and hypereutectoid compositions (6 and 17 wt% Cu) on TC4 (Ti6Al4V) fabricated by laser surface alloying (LSA) was investigated. LSAed TC4-Cu coatings displayed a higher tribo-corrosion resistance than that of pristine TC4 in 0.9 wt% NaCl solution at 37 °C owing to lower friction coefficient (COF), higher hardness and nobler open circuit potential (OCP). Tribo-corrosion of the LSAed TC4-Cu coatings was found to be dominantly attributed to mechanical wear, followed by wear-induced corrosion, while the electrochemical corrosion was negligible. The tribo-corrosion resistance of the LSAed TC4-Cu coatings was significantly enhanced because of the existence of the hard intermetallic phases (TiCu and TiCu), which effectively inhibit plastic deformation, reduce removal loss and galvanic effect between the worn and unworn regions during the tribo-corrosion process. The Cu-bearing TC4 coatings developed in this study demonstrate excellent tribo-corrosion resistance with effective anti-bacterial properties, suggesting their promising applications in the biomedical field.