Simulations of combustion in high-speed and supersonic flows need to account for autoignition phenomena, compressibility, and the effects of intense turbulence. In the present work, the evolution-variable manifold framework of Cymbalist and Dimotakis (“On Autoignition-Dominated Supersonic Combustion,” AIAA Paper 2015-2315, June 2015) is implemented in a computational fluid dynamics method, and Reynolds-averaged Navier–Stokes and wall-modeled large-eddy simulations are performed for a hydrogen–air combustion test case. As implemented here, the evolution-variable manifold approach solves a scalar conservation equation for a reaction-evolution variable that represents both the induction and subsequent oxidation phases of combustion. The detailed thermochemical state of the reacting fluid is tabulated as a low-dimensional manifold as a function of density, energy, mixture fraction, and the evolution variable. A numerical flux function consistent with local thermodynamic processes is developed, and the approach for coupling the computational fluid dynamics to the evolution-variable manifold table is discussed. Wall-modeled large-eddy simulations incorporating the evolution-variable manifold framework are found to be in good agreement with full chemical kinetics model simulations and the jet in supersonic crossflow hydrogen–air experiments of Gamba and Mungal (“Ignition, Flame Structure and Near-Wall Burning in Transverse Hydrogen Jets in Supersonic Crossflow,” Journal of Fluid Mechanics, Vol. 780, Oct. 2015, pp. 226–273). In particular, the evolution-variable manifold approach captures both thin reaction fronts and distributed reaction-zone combustion that dominate high-speed turbulent combustion flows.