To enhance the surface wear resistance of the Ti6Al4V alloy, diamond particles-reinforced Cu-based composite coatings (D500/D1000/D2000 coating: 500/1000/2000 mesh diamond: Cu-based alloy powder = 1:30 (wt%)) were fabricated by vacuum cladding. Cu-based alloys with liquid phase temperatures lower than the phase transition temperature of Ti6Al4V alloys were employed as cladding materials to avoid performance deterioration of Ti6Al4V substrates. The microstructure, mechanical properties, and dry-sliding tribological properties of the Cu-based composite coatings have been investigated systematically. The Cu-based composite coatings are composed of the ductile intermetallic compounds Ti3Sn and SnTi2 as the metal matrix, the hard and brittle intermetallic compounds CuTi, CuTi2, Ti(Cu, Al)2 and CuSn3Ti5, in situ generated TiC and the directly introduced diamond particle as the reinforced phases. In addition, a TiC hard phase protective layer was formed around the diamond particles, which retained the original properties of the diamond. The hardness of diamond particles-reinforced Cu-based composite coatings is much higher than that of the Ti6Al4V. Among them, the D2000 coating possesses the highest microhardness. The average Vickers hardness (HV0.5) on the coating surface and nanoindentation hardness (H) on the coating cross-section (the middle part without diamond particles) of the D2000 coating are 1329.8 HV0.5 and 16.87 GPa), which are 4–5 times higher than that of the Ti6Al4V substrate (333 HV0.5 and 3.37 GPa). Nevertheless, the D2000 coating (wear rate of 50.75 ×10−5 mm3/Nm) demonstrates slightly inferior tribological performance compared to the D500 coating. The wear rate of the latter is approximately 13.37 × 10−5 mm3/Nm, which is only 1/5.6 of the substrate (75.67 ×10−5 mm3/Nm). The larger the diamond particle size, the more the diamond serves as a bearing capacity support point to prevent the hard WC ball from further ploughing into the composite coating, and the better the wear resistance of the coating. Notably, D500 coating with excellent wear resistance has the potential for application in various fields of the machinery industry, marine engineering, and aerospace.