Successfully modeling the behavior of catalytic systems at different scales is a matter of importance not only for a fundamental understanding but also for a more rational design of catalysts and a more precise definition of the kinetic laws used as inputs in chemical engineering. We have developed here a multiscale modeling of the dehydration of isopropyl alcohol to propene and diisopropyl ether on γ-alumina catalysts, which clearly evidences and explains the central character of cooperative effects between coadsorbates in the kinetic network. The evolution of partial pressures with contact time was simulated using an original DFT-based microkinetic model based on a “macro site” centered on the main active site located on the (100) planes of alumina and comprising several neighboring adsorption sites. The formation of isopropyl alcohol–isopropyl alcohol or water–isopropyl alcohol dimers on the surface was required to correctly simulate the production of the minor product, diisopropyl ether, and the evolution of the product partial pressures at high conversion. DFT calculations were used to identify the structure of these dimers. In addition to entropic effects, the selectivity to ether is ruled by (i) stabilizing interactions between coadsorbed isopropyl alcohol or water molecules and the nucleophilic alcohol molecule reacting with the alcoholate intermediate, (ii) the formation of alcoholate–water dimers that selectively inhibit the formation of propene and increase the selectivity to ether at low conversion, and (iii) the reverse transformation of diisopropyl ether into propene and isopropyl alcohol that consumes ether at high conversion. The analytical expression of the reaction rate derived from this model and based on the existence of ensembles of interacting isopropyl alcohol and water molecules leads to a satisfactory modeling of the experimental kinetic measurements at all conversions.