Abstract Water isotopologue sieving has been flagged as one of the biggest challenges in modern separation technologies owing to their extremely similar physicochemical properties. As a benchmark candidate, current membrane separation suffers from inferior water isotopologue sieving as imposed by the failure of the size exclusion in conventional membrane separation. Herein, a facile approach is presented to elaborate MXene/Cellulose nanofiber (CNF) membranes featuring confined thermal‐recognized hydrogen bonding nanochannels, enabling highly‐selective, energy‐efficient and durable deuterium water sieving under low‐grade heat. The key to such membranes lies in the meticulous utilization of CNF‐enabled rich thermal‐recognized hydrogen bonds within nanochannels, which attract more deuterium water and water via deuterium bond and hydrogen bond (─OD/─OH) meanwhile thermally recognizing deuterium water with stable ─OD interaction to create more significant diffusion kinetic differences over water under low‐grade heat. It is demonstrated that the MXene/CNF membranes deliver an extraordinary separation factor as high as 5.2 yet demanding energy consumption as low as 2.9 GJ kg −1 , outperforming most of state‐of‐the‐art separation technologies. Moreover, the MXene/CNF membrane exhibits stable separation performance under long‐term operations and can be further integrated into multi‐stage separation device for augmenting separation and concentration of deuterium water, making it a step closer to the practical applications.