Amides functionalities are among the most widely found groups in biologically active molecules, and their selective catalytic reduction is an important target for synthetic methods. Recent advances in base metal catalysis have identified efficient systems for selective hydrogenolysis of the amide C–N linkage. This study examines in detail the mechanism for deaminative hydrogenation of formanilide and dimethylformamide (DMF) to the corresponding amines (aniline and dimethylamine, respectively) and methanol catalyzed by (iPrPNHP)Fe(H)2(CO) (iPrPNHP = HN{CH2CH2(PiPr2)}2) using density functional theory (DFT) calculations and microkinetic modeling. Following an initial hydrogenation of the amide carbonyl group, protonolysis of the C–N bond of the hemiaminal intermediate produces amine and formaldehyde, which is further hydrogenated to methanol. Remarkably, protonolysis of the C–N bond of the hemiaminal intermediate follows different pathways, depending on the nature of the substrate and the experimental conditions (presence or absence of cocatalyst) to yield the same products. In particular, cleavage of the C–N bond can be facilitated by either the metal catalyst or one of the organic species present (the amide substrate itself or an amide cocatalyst), with interesting consequences on the kinetics as evidenced by simulations using DFT calculated energy profiles for the entire pathway. This study reveals the subtle interplay between the nature of the substrate and the need for additives and changes the long-established principle that the hydrogenation of electron rich carbonyl substrates is governed by their carbonyl hydrogenation step and, therefore, only metal-hydride hydricity is relevant for catalyst design.