The oxidation of syngas mixtures was investigated experimentally and simulated with an updated chemical kinetic model. Ignition delay times for H2/CO/O2/N2/Ar mixtures have been measured using two rapid compression machines and shock tubes at pressures from 1 to 70 bar, over a temperature range of 914–2220 K and at equivalence ratios from 0.1 to 4.0. Results show a strong dependence of ignition times on temperature and pressure at the end of the compression; ignition delays decrease with increasing temperature, pressure, and equivalence ratio. The reactivity of the syngas mixtures was found to be governed by hydrogen chemistry for CO concentrations lower than 50% in the fuel mixture. For higher CO concentrations, an inhibiting effect of CO was observed. Flame speeds were measured in helium for syngas mixtures with a high CO content and at elevated pressures of 5 and 10 atm using the spherically expanding flame method. A detailed chemical kinetic mechanism for hydrogen and H2/CO (syngas) mixtures has been updated, rate constants have been adjusted to reflect new experimental information obtained at high pressures and new rate constant values recently published in the literature. Experimental results for ignition delay times and flame speeds have been compared with predictions using our newly revised chemical kinetic mechanism, and good agreement was observed. In the mechanism validation, particular emphasis is placed on predicting experimental data at high pressures (up to 70 bar) and intermediate- to high-temperature conditions, particularly important for applications in internal combustion engines and gas turbines. The reaction sequence H2+HO˙2↔H˙+H2O2 followed by H2O2(+M)↔O˙H+O˙H(+M) was found to play a key role in hydrogen ignition under high-pressure and intermediate-temperature conditions. The rate constant for H2+HO˙2 showed strong sensitivity to high-pressure ignition times and has considerable uncertainty, based on literature values. A rate constant for this reaction is recommended based on available literature values and on our mechanism validation.