The cooperative desorption of H2O and CO with 100% selectivity from the co-adsorbed cobalt oxide clusters CoxOyH2OCO+ [(x,y) = (3,3), (5,7), (6,9), and (9,12)] upon photo excitation at 355 nm was identified by mass spectrometry. In contrast, the sole desorption of CO dominated the mass spectra of CO3O3H2OCO+ upon collisional excitation by Xe at a wide range of center-of-mass collisional energies. The experiments and further kinetic modeling proposed the photo-catalytic coupling of H2O and CO on the cobalt oxide clusters. Combined with theoretical studies, a mechanism for the photo-catalytic coupling of dissociatively adsorbed H2O and CO is proposed.