Alcohol dehydration is of prominent relevance in the context of biomass conversion. This reaction can be efficiently catalyzed by alumina surfaces, but the nature of active sites, the mechanisms involved, and the key parameters to tune both the activity and the alkene/ether selectivity remain a matter of debate. In the present paper, isopropanol dehydration to propene and diisopropylether over γ-alumina, δ-alumina, and sodium-poisoned γ-alumina was investigated through a combined experimental and theoretical study. The experimental kinetic study shows that dehydration occurs following the same reaction mechanism on all materials, although γ-alumina activated above 450 °C exhibits the highest density of active sites and the highest global activity. Results suggest that all the reaction pathways involved in dehydration require the same set of adjacent active sites located on the (100) facets of γ-alumina. DFT transition-state calculations of the formation of propene and diisopropylether on the main terminations of alumina, (110) and (100), were also performed. The less activated pathways for both the formation of the olefin (E2 mechanism) and the formation of the ether (SN2 mechanism) were found on a AlV Lewis acidic site of the (100) termination, with calculated activation enthalpies (125 and 112 kJ·mol−1 for propene and diisopropylether formation, respectively) in good agreement with the experimental values (128 and 118 kJ·mol−1, respectively). The higher or lesser selectivity toward propene or ether appears to originate from significantly different activation entropies. The effect of coadsorbed sodium on the reaction is linked to the poisoning of Al sites by neighboring, Na-stabilized OH groups, but no influence of sodium on distant sites is evidenced. Reaction temperature is identified as the main key parameter to tune alkene/ ether selectivity rather than morphology effects, which in turn affect drastically the number of available active sites, and thus catalytic activity.