Development of stable high-voltage (HV), high capacity (HC) cathode oxides is indispensable to enhancing the performance of current high-energy-density (HED) lithium-ion batteries. Overstoichiometric, layered Li- and Mn-rich (LMR) composite oxides are promising materials for HV-HC cathodes for HED batteries; however, their practical use is limited. By probing the crystal structure, magnetic structure, and microstructure of the Li1.2Mn0.55Ni0.15Co0.1O2 LMR oxide, we demonstrate that the oxide loses its pristine chemistry, structure, and composition during the first charge-discharge cycle and that it proceeds through a series of progressive events that introduce impediments on the ion mobility pathways. We discovered i) the presence of tetrahedral Mn3+, interlayer cation intermixing, interface of layered-spinel, and structurally rearranged domains, cation segregation at an HV charged state, and ii) the loss of Li ions, inhomogeneous distribution of Li/Ni, and structurally transformed domains after the first discharge. The results will advance our fundamental understanding of the obstacles related to ion migration pathways in HV-HC cathode systems and will enable us to formulate design rules for use of such materials in high-energy-density electrochemical-energy-storage devices.