Biological fluoride ion channels are sub-1-nanometer protein pores with ultrahigh F− conductivity and selectivity over other halogen ions. Developing synthetic F− channels with biological-level selectivity is highly desirable for ion separations such as water defluoridation, but it remains a great challenge. Here we report synthetic F− channels fabricated from zirconium-based metal-organic frameworks (MOFs), UiO-66-X (X = H, NH2, and N+(CH3)3). These MOFs are comprised of nanometer-sized cavities connected by sub-1-nanometer-sized windows and have specific F− binding sites along the channels, sharing some features of biological F− channels. UiO-66-X channels consistently show ultrahigh F− conductivity up to ~10 S m−1, and ultrahigh F−/Cl− selectivity, from ~13 to ~240. Molecular dynamics simulations reveal that the ultrahigh F− conductivity and selectivity can be ascribed mainly to the high F− concentration in the UiO-66 channels, arising from specific interactions between F− ions and F− binding sites in the MOF channels.