A multistep methodology for the quantitative determination of rate constants of a detailed surface-reaction mechanism is proposed. As a starting point, thermodynamically consistent, coverage-dependent activation energies and heats of reactions were derived from the application of the unity bond index–quadratic exponential potential formulation, and initial estimates of the preexpontentials were obtained from transition-state theory or available experiments. Important feature identification analysis was performed to determine key kinetic parameters for various experiments. Model responses were parameterized in terms of these important parameters by polynomials and factorial design techniques, and these parameterized responses were subsequently used in simultaneous optimization through simulated annealing against different sets of experimental data to obtain a quantitative reaction mechanism that is valid over a wide range of operating conditions. The technique was successfully applied to the development of a comprehensive reaction mechanism for H2/air mixtures on polycrystalline Pt.