An experimental and computational approach is pursued to investigate the fracture mechanism of [0001] oriented zinc oxide nanowires under uniaxial tensile loading. A MEMS-based nanoscale material testing stage is used in situ a transmission electron microscope to perform tensile tests. Experiments revealed brittle fracture along (0001) cleavage plane at strains as high as 5%. The measured fracture strengths ranged from 3.33 to 9.53 GPa for 25 different nanowires with diameters varying from 20 to 512 nm. Molecular dynamic simulations, using the Buckingham potential, were used to examine failure mechanisms in nanowires with diameters up to 20 nm. Simulations revealed a stress-induced phase transformation from wurtzite phase to a body-centered tetragonal phase at approximately 6% strain, also reported earlier by Wang et al. (1) The transformation is partial in larger nanowires and the transformed nanowires fail in a brittle manner at strains as high as 17.5%. The differences between experiments and computations are discussed in the context of (i) surface defects observed in the ZnO nanowires, and (ii) instability in the loading mechanism at the initiation of transformation.