The presence of fluoride in drinking water can cause various diseases, such as dental fluorosis and skeletal fluorosis. The present study aims to intensify the fluoride removal using a rotating anode electro-coagulation (EC) reactor with providing the proper hydrodynamics conditions. This fluoride removal is modeled and optimized using Response Surface Methodology (RSM) and central composite design (CCD) with varying operational parameters (rotation speed: 20–80 RPM, current: 0.2–1.0 A, initial fluoride concentration: 8–40 mg/L and time: 15–75 min). The maximum fluoride removal is obtained as 96.87% (predicted) and 95.40% (experimental) for the optimized process parameters, initial concentration of 32 mg/L, 0.8 A current, 60 min, and 60 RPM of rotating speed. Kinetic analysis reveals that the removal process adheres to a second-order kinetic model, suggesting that the rate of fluoride removal is dependent on the concentration of fluoride ions present. Isothermal studies indicate that the effective sorption of fluoride onto the generated flocs follows a sips isotherm. The optimal cost analysis is carried out to determine the operational cost as 0.256 USD/m3 for F removal of 93.49% at initial concentration 24 mg/L, time 50 min, current 0.7 A, and rotation 70 rpm and presenting a cost-effective solution for fluoride mitigation. Further, characterizations of the resultant sludge through X-Ray Diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FTIR), and the Toxicity Characteristic Leaching Procedure (TCLP) confirmed the safe disposal potential of the sludge. The findings show a promising approach for fluoride removal, combining high efficiency, economic viability, and environmental safety.