Three-dimensional direct numerical simulations of spatially-developing mixing layers have been conducted and analyzed for three distinct values of the convective Mach number in both inert and reactive conditions. For reactive mixing layers, depending on the value of M-c, the thermal runaway occurs in either the mixing layer development zone (small value of Mc) or the fully developed turbulence region (larger value of Me). For the smallest values of Mc, there is a significant increase in temperature in the auto-ignition zone at values of the mixture fraction slightly lower than the most reactive one and for sufficiently small values of the scalar dissipation rate (SDR). The combustion mode here is predominantly non-premixed as deduced from the Takeno index. This is in sharp contrast with the complexity of the flow observed in the fully turbulent region where combustion takes place in a spotty regime featuring premixed pockets of fuel and oxidizer where the maximum levels of heat release follow quite closely the stoichiometric isoline. It is thus evidenced that, in the most compressible regime, where ignition occurs in the fully developed turbulent region, the contribution of premixed combustion becomes quite significant, a conclusion that differs from previous computational studies of supersonic combustion. Finally, the paper ends with the inspection of some assumptions that are currently retained in the modeling of supersonic reactive flows of non-premixed reactants. (C) 2016 The Combustion Institute. Published by Elsevier Inc. All rights reserved.