Hydrodynamics at the nanoscale involves both fundamental study and application of fluid and mass transport phenomena in nanometer-sized confinements. Nanopores in single-layer graphene can be highly attractive for exploring the molecular transport of gas and water molecules and hydrated ions at the ultimate scales of pore size and pore length. However, the experimental data is limited, and the state-of-the-art artificial nanopores still underperform compared to biological channels in cellular membranes. This dissertation focuses on developing ultimate graphene nanopore devices to study mass transport phenomena under controlled spatial confinement. We first investigated the kinetics of liquid–vapor transport from nanoscale confinements which is attractive for novel evaporation and separation applications; however, it is not explored at the ultimate confinement limit, i.e., at the atomic-thick and Å-scale nanopore placed at the liquid–vapor interface. We show that the evaporation flux from such nanopores increases with decreasing pore size by up to one order of magnitude relative to the bare liquid–vapor interface. Molecular dynamics simulations reveal that oxygen-functionalized nanopores render rapid rotational and translational dynamics to water molecules by reducing and shortening the lifetime of water–water hydrogen bonds. Graphene nanopores also enable the study of ion transport across sub-nanometer-scale 2D confinements. We produce tailor-made nanopores approaching the size of hydrated ions by decoupling the pore nucleation and expansion. Monovalent metal ions are efficiently sieved from divalent ions, with K+/Mg2+ selectivity up to 70 and Li+/Mg2+ selectivity up to 50, corresponding to a sieving resolution of 1 Å. Mitigating the non-selective pore formation further enhance the ion-sieving performance, reaching K+/Mg2+ selectivity up to 350 and Li+/Mg2+ selectivity up to 260. The pore size and structure allow adjusting the diffusion of ions across the nanopores, suggesting that the sterically induced partial dehydration process may play an important role in the observed cation selectivities. These selectivities were realized from centimeter-scale suspended graphene membranes, prepared in crack-free fashion by using dual layer reinforcement strategy where the first layer is 200-nm-thick nanoporous carbon (NPC) film hosting 20 nm pores which ensures a conformal contact and reinforcement of the graphene film and the second (top) layer is Nafion. Finally, a dual layer reinforcement is also demonstrated for preparing crack-free centimeter-scale gas separation membranes to utilize the full potential of graphene nanopores for energy-efficient applications. The bottom layer of the composite film is NPC film while the top layer is made of a 500-nm thick multi-walled carbon nanotube (MWNT) film with a pore size ranging from 200 to 300 nm. The obtained selectivities from crack-free centimeter-scale graphene membranes for H2/CH4 and H2/CO2 are 11–23 and 5–8, respectively, which is significantly higher than the corresponding Knudsen selectivities. Overall, this dissertation presents a graphene nanopore toolkit for studying fluid mechanics at the ultimate scales. The findings of enhanced water evaporation rate and ion selectivity using the nanopore platform could enrich our understanding of mass transport under extreme confinement and open new opportunities for a range of separation applications.