Herein, we report on highly H2O-selective derivatives of UiO-66-NH2 (UiO) metal-organic frameworks (MOFs) by enhancing the hydrophilic diffusion channels via a combination of hydrophilic modification and defect engineering. The parent framework, hydrophilic (carboxylated or sulfonated) derivatives, a defective derivative, and a defective and carboxylated derivative were prepared to investigate their structure-transport properties. Both experiments and dynamic functional theory simulations demonstrated that the carboxylation of UiO-66-NH2 is more desirable for H2O/N2 separation than sulfonation due to the enhanced hydrophilicity and less reduced surface area. A defect was induced by an acetic acid modulator, which decreased the hydrophilicity of the parent framework due to the methyl end groups; however, it increased the surface area by 38%, possibly enhancing the diffusion channels. In addition, thin-film nanocomposite (TFN) hollow fiber membranes, derived from the incorporation of carboxylated derivatives during interfacial polymerization, exhibited striped Turing structures on their surfaces, providing more efficient water transport channels. A subsequent TFN membrane containing defective and carboxylated derivatives showed the best H2O/N2 separation performance (H2O permeance of 2370 GPU and H2O/N2 selectivity of 769), suggesting a synergistic effect of hydrophilicity and defect-induced surface area. Our current work provides useful insights into fine-tuning the structural and textural properties of both MOFs and the associated composite membranes for air dehumidification. Display omitted •Carboxylation is more efficient for enhanced hydrophilicity of UiO-66-NH2 than sulfonation.•Acetic acid-induced defect engineering decreased hydrophilicity but enhanced H2O diffusion channels.•DFT simulations evaluated both hydrophilicity and diffusion channels of UiO-66-NH2 derivatives.•Carboxylated UiO-66-NH2 induced striped Turing structure on TFN surface, enhancing diffusion channels.•A synergistic effect of hydrophilic and defect modifications was demonstrated.