Forward osmosis (FO) is an emerging technology for environmental applications such as seawater desalination and wastewater treatment. However, the lack of long-term water stability and internal concentration polarization (ICP) phenomenon of FO membranes are the key challenges limiting its impact in real practice. In this study, we explore the use of water-stable metal-organic framework UiO-66 in different concentrations as fillers for the fabrication of high-performance and water-stable FO mixed-matrix membranes (MMMs) with mitigated ICP. The influences of UiO-66 on the phase inversion pathway and postinterfacial polymerization reaction cause changes in membrane morphology and chemistry, reducing the membrane structural parameter (S) and mitigating the ICP effect. As a result, the best performing FO membrane (6.5 wt % UiO-66) exhibits a 50% increased water flux over the pristine membrane, when deionized water and 1 M NaCl are used as the feed and draw solutions, respectively. The extent of ICP mitigation has been quantified by the solution-diffusion model, demonstrating effective control by the presence of UiO-66. Because of the excellent water stability of UiO-66, no significant degradation of water permeability is observed over 72 h operation. Therefore, the newly designed UiO-66 incorporated FO MMMs are of great interest and have potential for advancing membrane performances in water filtration and related environmental practice.