A novel Ti35Zr15Nb25Mo15Ta10 high‐entropy alloy has been designed, fabricated, and characterized as a viable substitute for the conventional Ti‐6Al‐4V alloy in biomaterial applications. Alloy design is conducted based on various parameters including mixing enthalpy (ΔHmix), omega parameter (Ω), delta parameter (δ), valence electron concentration (VEC), and biocompatibility aspects of its constituent elements with CALPHAD approach. The fabricated Ti35Zr15Nb25Mo15Ta10 alloy demonstrated a body‐centered‐cubic (BCC) solid solution phase with no evidence of intermetallics. Nanoindentation investigations exhibited high hardness of ≈5.1 GPa and a young modulus of ≈140 GPa. The alloy proposed better surface properties and tribological behaviour in comparison with the Ti‐6Al‐4V alloy in dry and wet (under PBS solution) conditions. Furthermore, the newly designed alloy revealed promising behaviour after investigation of in‐vitro biocompatibility compared to the Ti‐6Al‐4V alloy. These initial benefits of the Ti35Zr15Nb25Mo15Ta10 alloy concerning mechanical properties and wear resistance over the conventional Ti‐6Al‐4V alloy present an avenue for exploring novel orthopedic implant alloys.