Low flow resistance is essential for the design of nanofluidic platforms. Here, we present a comparative atomic-level study analyzing the fundamentals of water flow enhancement in a polymeric nanochannel due to the implementation of monatomic thick coatings—specifically, graphene and hexagonal boron nitride (hBN). Our results obtained employing large scale non-equilibrium molecular dynamics simulations and continuum models, revealing significant values of slip lengths of ∼29 and ∼6 nm for graphene- and hBN-coated nanochannels, respectively. Equilibrium molecular dynamics simulations, using the Green-Kubo relation, show the significant effect that the partial charges of hBN coating layer have on the water-wall friction. In addition, consistent values of the slip length are obtained from independent sets of equilibrium and non-equilibrium molecular dynamics simulations, confirming that the computed interfacial friction coefficients hold across flow regimes where water molecules no longer occupy the most energetically stable zones at the interface. Hence, the lower interfacial friction observed in the graphene-coated channel leads to a higher water flow enhancement than the one computed in the hBN-coated channel. We also show that the natural undulations of two-dimensional honeycomb-like materials, implemented as wall coatings, remain largely unhindered due to strong interfacial coupling facilitated by π − π stacking between the underlying aromatic polymer substrate and coating monolayers. This is particularly relevant for graphene coatings, which display significant out-of-plane thermal rippling that further enhances water flow. This observation is supported by a stronger atomic-scale vibrational coupling at the water-graphene interface compared to that computed at the water-hBN interface.