Lithium-rich layered oxides (LLOs) are considered as one of the most potential layered cathode materials due to their high discharge specific capacity, low cost, and environmental friendliness. However, the decomposition of electrolytes at high voltages (4.7 V) limits the commercial application of LLOs. Furthermore, to meet the demand for high energy density, lithium nickel cobalt manganese oxides (NCMs) need to improve their working voltage. In limited conditions, all LLOs and NCMs need to be used under the medium− high (4.4−4.6 V) cutoff voltage. Herein, we compare the performance of LLOs and NCMs in the voltage window with a medium−high cutoff voltage. Results show that after 100 cycles at high temperature (45 °C), the capacity retention rate of LLO is 98.68%, while that of NCMs is 78.15−96.93%. Differential scanning calorimetry reveals that the exothermic temperature of LLO is increased by 60−100 °C, and thermal release is reduced by 33−93%. LLOs have obvious advantages under medium−high voltages and a promising application prospect. This work systematically analyzes and compares LLOs and NCMs under medium−high voltage, providing guidance for the industrialization of LLOs.