Practical copper (Cu)-based catalysts for the water–gas shift (WGS) reaction was long believed to expose a large proportion of Cu(110) planes. In this work, as an important first step toward addressing sulfur poisoning of these catalysts, the detailed mechanism for the splitting of hydrogen sulfide (H2S) on the open Cu(110) facet has been investigated in the framework of periodic, self-consistent density functional theory (DFT-GGA). The microkinetic model based on the first-principles calculations has also been developed to quantitatively evaluate the two considered decomposition routes for yielding surface atomic sulfur (S*): (1) H2S → H2S* → SH* → S* and (2) 2H2S → 2H2S* → 2SH* → S* + H2S* → S* + H2S. The first pathway proceeding through unimolecular SH* dissociation was identified to be feasible, whereas the second pathway involving bimolecular SH* disproportionation made no contribution to S* formation. The molecular adsorption of H2S is the slowest elementary step of its full decomposition, being related with the large entropy term of the gas-phase reactant under realistic reaction conditions. A comparison of thermodynamic and kinetic reactivity between the substrate and the close-packed Cu(111) surface further shows that a loosely packed facet can promote the S* formation from H2S on Cu, thus revealing that the reaction process is structure sensitive. The present DFT and microkinetic modeling results provide a reasonably complete picture for the chemistry of H2S on the Cu(110) surface, which is a necessary basis for the design of new sulfur-tolerant WGS catalysts. © 2013 Wiley Periodicals, Inc.