We conducted a systematic analysis of water networking inside smooth hyperboloid hydrophobic structures (cylindrical, barrel, and hourglass shapes) to elucidate the role of water hydrogen bonding on the transport of small hydrophobic molecules (ligands). Through a series of molecular dynamics simulations, we established that a hydrogen-bonded network forming along the centerline resulted in a water exclusion zone adjacent to the walls. The size of the exclusion zone is a function of the geometry and the nonbonded interaction strength, defining the effective hydrophobicity of the structure. Exclusion of water molecules from this zone results in lower apparent viscosity, leading to acceleration of ligand transport up to 7 times faster than that measured in the bulk. Transport of ligands into and out of the hydrophobic structures was shown to be controlled by a single water molecule that capped the narrow regions in the structure. This mechanism provides physical insights into the behavior and role of water in the bottleneck regions of hydrophobic enzyme channels. These findings were then used in a sister publication [Escalante, D. E., et al.Comput. Struct. Biotechnol. J.201917757760] to develop a model that can accurately predict the transport of ligands along nanochannels of broad-substrate specificity enzymes.