Understanding how physicochemical properties of materials affect the oxygen evolution reaction (OER) has enormous scientific and technological implications for the OER electrocatalyst design. We present our investigation on the role of strain on the surface-oxygen interaction and the OER on well-defined single-termination SrIrO3 films. Our approach employs a combination of molecular-beam epitaxy, electrochemical characterizations, ambient-pressure X-ray photoelectron spectroscopy, and density functional theory (DFT). We find that inplane compressive strain weakens the surface oxygen binding strength on SrIrO3; however, it has a negligible effect on the surface oxygen electroadsorption and the OER. We explain this observation, which goes against a commonly held intuition that a change in the surface oxygen binding strength should influence surface oxygen electroadsorption and OER by recognizing that the trend in surface oxygen adsorption measured in the gas phase does not account for the presence of water in the surface oxygen electroadsorption. Inclusions of surface water molecules allow DFT to qualitatively reproduce the electroadsorption trend, highlighting the importance of surface water in the surface-oxygen interaction. Our finding suggests that a commonly held assumption between surface oxygen binding strength (in vacuum, no water) and electroadsorption (requiring water) is not always a simple one-to-one description and calls for a more in-depth investigation on the structure of water at electrochemical interfaces. © 2018 American Chemical Society.