In this work, we present a combined experimental and theoretical investigation of stable MgAl2O4-supported Rh and Ir catalysts for the steam methane reforming (SMR) reaction. Catalytic SMR performance for a series of noble metal catalysts supported on MgAl2O4 spinel has been evaluated at 873-1123 K. The turnover rate at 873 K follows the order: Pd > Ir > Pt similar to Rh > Ru > Ni. However, Rh and Ir are found to have the best combination of activity and stability for SMR in the presence of simulated biomass-derived syngas where highly dispersed similar to 2 nm Rh and similar to 1 nm Ir clusters are identified on the MgAl2O4 spinel support. Scanning Transmission Electron Microscopy (STEM) images show that this excellent dispersion is maintained even under high-temperature conditions (e.g., at 1123 K in the presence of steam), while larger particle sizes of Rh and particularly Ir are observed when supported on Al2O3. These observations are further confirmed by ab initio molecular dynamic (AIMD) simulations, which find that similar to 1 nm Rh and Ir particles (50-atom cluster) bind strongly to the MgAl2O4 surface via a redox process. The strong metal-support interaction between the spinel support and Rh or Ir helps anchor the metal clusters and reduce the tendency to form larger particle sizes. Density functional theory (DFT) calculations suggest that these supported smaller Rh and Ir particles have a lower work function than larger more bulk-like ones, which enables them to activate both water and methane more effectively than larger particles, yet have a minimal influence on the relative stability of coke precursors. In addition, theoretical mechanistic studies are used to probe the relationship between structure and reactivity. Consistent with the experimental observations, our theoretical modeling results also suggest that the small spinel-supported Ir catalyst is more active than the counterpart Rh catalyst for SMR. (C) 2014 Elsevier Inc. All rights reserved.