This work presents a numerical study of supersonic hydrogen–air mixing layers, in both shock-free and shock-assisted configurations, using high-fidelity simulations performed with the computational fluid dynamics solver CREAMS, which includes detailed diffusion transport and chemical kinetics. The canonical two-dimensional mixing layer is analysed to assess the influence of inlet profiles and shock-induced flow structures on auto-ignition behaviour. In the absence of shocks, self-similar inlet profiles – accounting for Soret, Dufour and viscous dissipation effects – exhibit distinct ignition characteristics compared to standard hyperbolic tangent profiles. For non-isothermal (hot–cold) streams, the ignition distance remains nearly unaffected by the inlet profile, confirming a primarily thermal control of ignition; however, the ignition kernel shifts towards the hotter stream due to enhanced species diffusion. In contrast, for isothermal configurations, the self-similar profile significantly accelerates ignition, reducing the ignition distance by over 1 cm, primarily through viscous heating effects. Under shock impingement conditions, increasing the incident shock angle strengthens the reflected expansion wave, locally cooling the upper stream and delaying ignition, with complete ignition failure observed for sufficiently low inclined shocks. Near marginal conditions, only the self-similar profile sustains stable ignition by promoting higher initial mixedness. The results provide a detailed database and physical insight into how inlet thermochemical structure and shock–mixing layer interactions govern ignition distances and flame stabilisation in supersonic reactive flows