The interfacial reaction layers in the Ti/ZrO2 diffusion couples, isothermally annealed in argon at temperatures ranging from 1100° to 1550°C for 6 h, were characterized using scanning electron microscopy and transmission electron microscopy, both attached with an energy-dispersive spectrometer. Very limited reaction occurred between Ti and ZrO2 at 1100°C. A β′-Ti(Zr, O) layer and a two-phase α-Ti(O) +β′-Ti(Zr, O) layer were found in the titanium side after annealing at T ≥ 1300°C and T ≥ 1400°C, respectively. A three-phase layer, consisting of Ti2ZrO+α-Ti(O, Zr)+β′-Ti (O, Zr), was formed after annealing at 1550°C. In the zirconia side near the original interface, β′-Ti coexisted with fine spherical c-ZrO2-x, which dissolved a significant amount of Y2O3 in solid solution at T ≥ 1300°C. Further into the ceramic side, the α-Zr was formed due to the exsolution of Zr out of the metastable ZrO2-x after annealing at T ≥ 1300°C: the α-Zr was very fine and dense at 1300°C, continuously distributed along grain boundaries at 1400°C, and became coarsened at 1550°C. Zirconia grains grew significantly at T ≥ 1400°C, with the lenticular t-ZrO2-x being precipitated in c-ZrO2-x. Finally, the microstructural development and diffusion paths in the Ti/ZrO2 diffusion couples annealed at various temperatures were also described with the aid of the Ti-Zr-O ternary phase diagram.