We present a two-stage fabrication method for Zn2TiO4−ZnO nanowire axial heterostructures using the site-specific deposition of TiO2 on the tips of ZnO nanowires, followed by an annealing process. As revealed by the electron microscopy investigation, the cubic spinel Zn2TiO4 single crystal heads possess two kinds of oriented relationships with ZnO nanowires after high-temperature reaction. The reaction between TiO2 nanoparticles and ZnO nanowires shows a unilateral diffusion characteristic of ZnO into TiO2 which provides a useful method for rational design and fabrication of nanostructures based on nanostructured phase transformation.