Desalination provides an effective method to meet the worldwide freshwater crisis. Reverse osmosis (RO) based on polyamide (PA) thin-film composite (TFC) membranes have dominated desalination area with the enhancing desalting properties and decreasing energy consumption. However, it is still an urgent affair for the researchers all over the world to explore more advanced RO desalination materials and procedures to further enhance the popularization of desalination, among which development of superior membranes with as far as possible high water flux and satisfied salt rejections are particularly important. Two-dimensional (2D) nanoporous membranes with sub-nanopores, typically represented by graphene and its derivatives accompanied with some analogues such as molybdenum disulfide (MoS2), have displayed great potential and attracted vast interest in designing such kinds of desalination membranes. Actually, 2D nanoporous membranes might have opened a new era in desalination membranes fabrication and demonstrated brilliant future. Given this, in this review paper we reviewed and discussed the development of 2D nanoporous membranes with sub-nanopores on desalination with emphasis in simulations coupled with experimental studies. Besides, the feasibility and future directions of 2D nanoporous membranes are prospected. We sincerely hope that this paper could provide clues and insights for the future exploration of novel desalination membranes, and further contribute to the advance of desalination membranes synthesis and large-scale production.