Fluoride pollution is a serious environmental problem that is a risk to human health. Hence, the effective elimination of fluoride is urgent. Herein, a novel trimetallic Zr–La–Ce MOF was fabricated with a hydrothermal method and adapted to eliminate fluoride from water media. Characterization showed that the adsorbent presented a flower-like morphological structure with a large specific surface area of 682 m2 g–1. The adsorption property was further evaluated by examining the impact of fluoride concentration, solution pH, and coexisting anions. The adsorption capacity of Zr–La–Ce MOFs is above 110 mg g–1 at pH 2–9, indicating that Zr–La–Ce MOFs have a wide applied pH range, and the coexisting ions have a tiny impact on the fluoride removal performance, demonstrating an excellent fluoride selectivity. The sorption process adhered well to the Langmuir model and pseudo-second order kinetic model, and the maximum Langmuir sorption capacity was 167.61 mg g–1. Practical application investigation, regeneration performance evaluation, and safety experiments demonstrated that the Zr–La–Ce MOFs had excellent recycling performance, with the treated water lower than 1 mg L–1, and no precipitation of metal ions, which has certain potential for practical application and can provide insights and references for the preparation of multimetal MOFs.