The mechanism of hydrogen embrittlement (HE) is highly sensitive to material composition, microstructure, local hydrogen concentration, hydrogen pressure, and loading conditions. Although experimental studies have consistently demonstrated that high-strength steels under tensile stress are susceptible to mechanical degradation from hydrogen uptake, the atomic-scale mechanisms underlying stress- and strain-induced HE remain unclear. Previous atomic-scale, first-principles investigations have primarily focused on two areas: (1) the role of individual alloying elements in modulating hydrogen diffusion in metallic systems; (2) the influence of prestrain (ε) on hydrogen diffusion in pure or homogeneous metals. However, first-principles studies that explicitly address the combined effects of ε, microstructural heterogeneity, and H are lacking. To elucidate the interaction between Cr–Mo alloyed steel and H under ε, we employ density functional theory for probing their tripartite interplay in α-Fe. Our analysis focuses on four critical aspects: site geometry, energetics, electronic structure, and diffusion barriers. Results show that H atoms consistently favor tetrahedral (T) sites over octahedral (O) sites, regardless of applied ε. In the Cr–Mo codoped system, H occupancy at pure Fe sites is energetically more favorable than at Fe–Cr sites. The latter induces substantial cohesive energy loss, thereby increasing HE susceptibility. Importantly, Mo incorporation considerably reduces the number of Fe–Cr sites accessible to H near Cr atoms, effectively mitigating HE. Application of ε lowers the crystal binding energy (E_b), with the magnitude of reduction scaling positively with |ε|. Hydrogen incorporation further reduces E_b but does not alter the overall ε-dependent trend. Cr–Mo codoping breaks the lattice symmetry. Under the combined effects of ε and H, T sites exhibit marked anisotropy in geometric parameters (metal—H and metal—metal distances), energetic descriptors (binding and solution energies), and electronic structure metrics (Bader charge and integrated crystal orbital Hamilton population). This anisotropy drives directionally dependent H diffusion in the bulk. In addition, H preferentially migrates from Fe–Cr sites toward pure Fe sites, whereas the reverse process is kinetically hindered. Compressive ε elevates the diffusion barrier for H migration perpendicular to the ε direction, thereby suppressing external H ingress and internal bidirectional diffusion along this path. This reduces the likelihood of H populating high-risk Fe–Cr sites and thus alleviates HE. In stark contrast, tensile ε promotes H accumulation in planes perpendicular to ε, accelerating crack nucleation and brittle fracture.