Cesium fluoride is widely used in organic synthesis as a source of fluoride ions due to its high solubility in polar solvents and strong nucleophilic activity. It is particularly effective in desilylation reactions, where it removes silyl protecting groups from alcohols, amines, and other functional groups under mild conditions, including the hydrolysis of silyl enol ethers to carbonyl compounds. It also facilitates fluorodesilylation to introduce fluoride groups. It serves as a catalyst or reagent in nucleophilic substitution reactions, including SN2 reactions and fluorination processes, such as the synthesis of ¹⁸F-labeled compounds for positron emission tomography (PET) imaging in medicine.

In materials science, cesium fluoride is employed in the fabrication of semiconductor devices, perovskite solar cells, and electronic circuit boards, where it improves electron transport and enhances device efficiency. It is also used in the preparation of other fluorinated compounds and in electrochemical applications involving fluoride ion conduction. Its low lattice energy and high ionic character make it especially useful in solid-state chemistry and in promoting solid-liquid phase transfer catalysis. Additionally, it functions as a catalyst or niche additive in the precise synthesis of specialty compounds.