The primary and secondary deuterium kinetic isotope effects as well as leaving-group fluorine kinetic isotope effects have been calculated for the base-promoted elimination of hydrogen fluoride from 4-fluoro-4-(4′- nitrophenyl)butane-2-one in 75% aqueous methanol solution. The elimination was studied for both formate and imidazole as the catalytic base; and reactant and transition state structures and vibrational frequencies have been calculated by including the base explicitly and by including the solvent by an implicit solvation model that includes both electrostatics by class IV charges and first-solvation-shell effects by atomic surface tensions. We used the M06-L density functional for all calculations. The optimized stationary points, the geometry changes along the solution-phase minimum free energy path, and the solution-phase free energy profile indicate that the elimination reaction occurs concertedly but asynchronously via an E1cb-like transition state. Reaction rates were calculated by the equilibrium solvation path method, using variational transition state theory with multidimensional tunneling. The primary deuterium kinetic isotope effects are calculated to be large: 1.67 and 5.13 for formate and imidazole, respectively. The corresponding C4-secondary deuterium kinetic isotope effects are 1.044 and 1.044, and the leaving group fluorine kinetic isotope effects are respectively 1.020 and 1.015.