Metal–organic frameworks (MOFs) are versatile nanoporous materials that have gained significant interest as low heat capacity, high selectivity sorbents for CO₂ capture applications. Large-scale atomistic simulations for identifying high-performance MOFs are possible, but are limited to systems for which existing molecular mechanics force fields describe the interactions between the guest and framework atoms with sufficient accuracy. However, standard force fields are not applicable to cases involving coordinatively unsaturated metal centers that can strongly bind specific sorbate molecules. It has been previously shown that improved force fields can be derived from quantum mechanical calculations. In this work, we derived force fields for an isostructural series of MOFs, M-MOF-74, where M = Mn, Co, Ni, and Cu, from first principles. Monte Carlo calculations in the Gibbs ensemble were used to calculate the CO₂ adsorption isotherms in order to assess the quality of the derived force field parameters and to determine a generally applicable procedure for obtaining a reliable force field for a targeted MOF and adsorbate system. The computed CO₂ adsorption isotherms for the different M-MOF-74 members agree with experimental measurements at low loading and show that Ni-MOF-74 possesses the highest affinity toward CO₂ and Cu-MOF-74 the weakest. In addition, we explored the source of open metal site and pore inaccessibility in these materials and quantified its impact on adsorption, especially the discrepancies often observed between experiments and simulations at high loadings.