We investigated the wetting of a high-entropy rare-earth oxide, (La0.2Nd0.2Sm0.2Eu0.2Gd0.2)2Zr2O7, by a molten 71Ag–27Cu–2Ti (in wt%) alloy using a modified sessile drop method at 1073–1273 K. The wettability shows a first increase and then decrease with increasing temperature, depending on the competition among the adsorption and diffusion of active Ti atoms towards triple line, the consumption of Ti due to interfacial reaction and the migration of oxygen from the substrate bulk to the interface. In addition, the La cations in the high-entropy substrate exhibited noticeable outward diffusion while the other rare-earth cations remained stable due to their different bonding strengths in the lattice. Despite the occurrence of interfacial reaction and selective diffusion, the substrate maintained the high-entropy structure after the reactive wetting.