The sequence of addition of promoters (K, Cu, Ru) to Fe-Zn oxides markedly influences Fischer-Tropsch synthesis rates, which reached a maximum value for catalysts with Fe/Cu and Fe/K ratios of 0.03 and 0.06, respectively. A kinetic and mechanistic study led to a sequence of elementary steps that describes the synthesis of hydrocarbons and the removal of oxygen as H2O or CO2. These steps consider parallel C-O activation steps aided and unaided by co-adsorbed hydrogen and resolve remaining inconsistencies about the hydrogen dependence of hydrocarbon synthesis and oxygen removal rates. The extension of these conclusions to cobalt-based catalysts suggests that kinetically-relevant CO dissociation steps proceed predominantly with the assistance of co-adsorbed hydrogen. The inverse kinetic isotope effects measured on both Fe and Co catalysts are consistent with this proposal. These data are complemented with periodic, self-consistent, DFT-GGA estimates used to suggest minimum energy paths for these elementary steps on Fe(110) and Co(0001) surfaces. These simulations focus specifically on the dissociation of C-O and the hydrogenation of relevant surface intermediates and also explore the consequence of H/D isotopic substitution on their rate constants. Taken together, this combined approach allows us to comment on the nature and kinetic relevance of the formation and cleavage of specific chemical bonds in a manner inaccessible to separate experimental and theoretical inquiry.