Using a two-step approach, which includes a screening method (based on Morris Method) followed by global sensitivity analysis (based on High-Dimensional Model Representation), the uncertainty-based sensitivity of binary diffusion coefficients and chemical kinetic parameters over the full uncertainty range are presented for both simulations of premixed and non-premixed hydrogen-oxidizer-diluent mixtures. By implementing realistic uncertainty factors for binary diffusion coefficients and chemical kinetic parameters, the measured experimental uncertainty of laminar flame propagation velocity (S-L(0)) is shown to be greater than the uncertainty on predicted S-L(0) propagated from the binary diffusion coefficient parametric space. For 1 and 15 atm laminar flame speed simulations, the propagated uncertainties (epsilon) due to separate perturbation of the diffusion coefficients and chemical parameters are 3-5% and 12-41% respectively. The values of epsilon for the extinction strain rate at 1 atm are 6-8% and 19-28%. In premixed flames, the propagated uncertainty of chemical parameters increases with pressure, whereas the propagated uncertainty of binary diffusion coefficients is not affected. Based on current flame property measurements (about 5-10%), these results indicate that the fundamental flame properties clearly offer the possibility of reducing the chemical kinetic parameter uncertainties but marginal or no possibility of reducing the diffusion coefficient uncertainties. (C) 2012 The Combustion Institute. Published by Elsevier Inc. All rights reserved.