Fluoride-ion batteries are an attractive energy storage concept analogous to lithium-ion batteries but feature an inverted paradigm where anions are the principal charge carriers. Insertion hosts that can reversibly insert fluoride ions at room temperature are exceedingly sparse. Here, we report that topochemical insertion of fluoride ions in FeSb 2 O 4 involves Fe 2+ /Fe 3+ redox but is mediated by multi-center synergies between iron and antimony centers. Separation of the redox center from the p-block coordination site alleviates structural strain by enabling compensatory contraction and expansion of FeO 6 and SbO 3 polyhedra, respectively. p-block electron lone pairs play a critical role in weakening anion-lattice interactions, enabling reversible fluoride-ion diffusion across microns. The results illuminate the key principle that interactions traceable to stereoactive lone pairs can be used to mediate anion-lattice interactions and suggest that anion insertion hosts can be designed by pairing redox-active transition metals with p-block cations bearing stereochemically active electron lone pairs. Topochemical insertion of fluoride ions is mediated by synergies between Fe and Sb centers p-block electron lone pairs weaken anion-lattice interactions X-ray ptychography imaging demonstrates bulk fluoride-ion diffusion Sb 5 s 2 electron lone pairs enable fluoride-ion deinsertion and facile diffusion Despite several decades of research, fundamental design principles for anion insertion in crystalline lattices remain poorly explored. Zaheer et al. provide a fundamental design principle based on electronic structure considerations that allows use of anions (fluoride ions) instead of cations for electrochemical energy storage.