Lithium-rich layered oxides having compositions of Li1+y M1−y O2 (M = Co, Mn, and Ni) have become attractive cathode materials for high energy density and high voltage lithium ion batteries for electric vehicle (EV) applications. However, their utility in EVs suffers from both voltage and capacity fade. The voltage fade is related to structural transformation in these lithium-rich oxides and must be thoroughly understood. In this work, we have utilized in situ X-ray diffraction in order to monitor these structural transformations during high voltage (4.8 V) cycling of a lithium- and manganese-rich Li1.2Co0.1Mn0.55Ni0.15O2 oxide cathode, which has not been reported previously. The lattice parameters of the cathode were monitored for first cycle and compared with the subsequent cycles. Based on our results, the c-lattice parameter increases during the course of initial charging and eventually decreases upon charging beyond 4.4 V, which verifies lithium extraction occurs from transition metal layers due to activation of Li2MnO3 phase at high-voltage. The fact that the a-lattice parameter remains constant at the first cycle plateau region indicates oxygen loss from the structure during first cycle charging which is attributed to irreversible capacity obtained from first cycle. For first and subsequent cycles, the c-lattice parameter increases during discharge up to 3.5 V and below 3.5 V, the decrease in those values was observed. After subsequent cycling, (440) cubic spinel reflections were observed during low voltage discharge process, which reveals a layer to spinel-like phase transformation in the lattice and is thought to be the reason for the observed voltage fade. A significant decrease in monoclinic phase was observed after subsequent cycles and is believed to contribute to the structural instability and capacity fade after repeated cycling.