Nickel (Ni)-rich cathode materials have become promising candidates for the next-generation electrical vehicles due to their high specific capacity. However, the poor thermodynamic stability (including cyclic performance and safety performance or thermal stability) will restrain their wide commercial application. Herein, a single-crystal Ni-rich LiNi0.83Co0.12Mn0.05O2 cathode material is synthesized and modified by a dual-substitution strategy in which the high-valence doping element improves the structural stability by forming strong metal–oxygen binding forces, while the low-valence doping element eliminates high Li+/Ni2+ mixing. As a result, this synergistic dual substitution can effectively suppress H2-H3 phase transition and generation of microcracks, thereby ultimately improving the thermodynamic stability of Ni-rich cathode material. Notably, the dual-doped Ni-rich cathode delivers an extremely high capacity retention of 81% after 250 cycles (vs. Li/Li+) in coin-type half cells and 87% after 1000 cycles (vs. graphite/Li+) in pouch-type full cells at a high temperature of 55 °C. More impressively, the dual-doped sample exhibits excellent thermal stability, which demonstrates a higher thermal runaway temperature and a lower calorific value. The synergetic effects of this dual-substitution strategy pave a new pathway for addressing the critical challenges of Ni-rich cathode at high temperatures, which will significantly advance the high-energy-density and high-safety cathodes to the subsequent commercialization.