Given Fe is a low-cost earth-abundant element, there is a need to develop novel Fe-based metal hydrides. The conventional Fe-based hydrides consist of at least one metal with high hydrogen affinity. To synthesize novel low-affinity Fe-based hydrides, the high-pressure and high-temperature method is currently being used. The microstructure is known to influence the de-/hydrogenation processes in metal hydrides. However, in the context of low-affinity Fe-based hydrides, the role of the initial multi-phase microstructure is unknown, which is the objective of the current work. We investigate three as-cast Fe–Mo binary alloys: Fe0.33Mo0.67, Fe0.5Mo0.5, and Fe0.67Mo0.33. Firstly, we first explain in detail the formation mechanisms of the non-equilibrium initial as-cast microstructures caused by the sluggish diffusion of Mo. Subsequently, we present the phase transformations and microstructure evolution during the hydrogenation, depressurization, and aging of Fe–Mo alloys. We demonstrate that each phase in the initial microstructure act as an independent phase during hydrogenation.