Computational and experimental investigations have previously revealed that the surface chemistry of metal nanoparticles used as fuel cell electrocatalysts can influence both wetting by water as well as the morphology of deposited solid polymer electrolytes. However, the impact of nanoparticle surface chemistry on practical fuel cell operation at high current load is unknown. Mass-transport and ohmic overpotentials are found to dominate performance at high load, hindering the impact of significant recent advances in electrocatalytic activity during practical operation. Prior investigations with operating fuel cells have typically focused on altering the distribution and content of ionomer in the electrode as well as the introduction of hydrophilic agents but often neglect the role of metal nanoparticle surface chemistry. In this investigation, we contrast the electrocatalytic and practical fuel cell performance of commercial carbon-supported Pt nanoparticles to carbon-supported and unsupported Pt and Pt-alloy nanoparticles synthesized via a metal-redox scheme that utilizes stabilizing inorganic ligands to alter the nanoparticle surface chemistry. ¹¹⁹Sn Mossbauer spectroscopy, X-ray Absorption, and X-ray Scattering are used to characterize ligand surface chemistry and structure. The catalysts are also characterized with respect to their Pt surface atom coordination using electrochemical stripping of Bi and Ge adatoms. In addition, the surface wettability of the various catalyst components (support, ionomer, metal nanoparticles) is differentiated using dynamic contact angle analysis. We determine that hydrogen/air fuel cell operation at high load is well-correlated to the surface chemistry of the nanoparticles. For a given surface atom coordination and ORR mass activity, catalysts produced via hydrophilic surface ligands permit the electrodes to operate under substantially drier conditions. Comparable single cell maximum power of 0.5 W/cm2 is realized at 40% inlet gas humidification for nanoparticles synthesized utilizing hydrophilic surface ligands versus 80% when an industrial precipitation approach is used for Pt nanoparticles ~3 nm, independent of ionomer loading. A remarkable swap in polarization behavior with humidification is observed. Correlations of fuel cell humidification requirements to alternate nanoparticle morphologies with varying surface atom coordination, inorganic ligand structures, and wetting behavior are described.