A series of single-crystal, Ni-rich Li[NixCoyMn1–x–y]O2 (NCM) cathodes (x = 0.7, 0.8, and 0.9) with particle diameters of ∼3 μm are systematically compared with polycrystalline cathodes with corresponding Ni contents. Despite their high resistance to microcracking, the electrochemical performances of single-crystal NCM cathodes, in terms of capacity and cycling stability, are inferior to those of polycrystalline NCM cathodes. In situ XRD and TEM analyses reveal that the lithium concentrations in single-crystal NCM cathodes become spatially inhomogeneous during cycling; this phenomenon is exacerbated by high C rates and Ni contents, resulting in the coexistence of phases with widely different unit cell dimensions within a single cathode particle. This coexistence of two phases induces nonuniform stress that generates structural defects, impairing the diffusion of lithium ions and, eventually, leading to rapid capacity fading.