Titanium alloys have been widely used for medical devices and structural applications. However, conventional titanium alloys often suffer from low resistance to wear, particularly at elevated temperatures. Herein, an equiatomic TiMoNb compositionally complex alloy (CCA) is shown to exhibit wear resistance comparable to alumina at room temperature (RT). Even at 600 °C, the alloy still shows an extremely low wear rate of the order of 10 mm/(N·m). The remarkable wear resistance is achieved via tuning the interfacial structure and chemistry in TiMoNb CCA, including nanostructuring, titanium segregation at the grain boundaries, and the formation of a high density of nanoscale coherent Ti-rich precipitates with cube-on-cube orientation relationship with the ultrafine-grained matrix. The present results provide significant insights into the design of novel alloys for service in harsh environments.