Density functional theory calculations and reactivity data were used to examine the mechanism of alcohol dehydration on Keggin-type polyoxometalate (POM) catalysts and the influence of the POM composition and the degree of substitution of the alcohol on kinetically relevant elimination steps. Dehydration was found to proceed through E1 pathways in which the alcohol CsO bond is cleaved heterolytically via a carbeniumion transition state. Dehydration rates were found to depend on the elimination rate constant and the equilibrium constant for the formation of unreactive alcohol dimers. E2-type elimination transition states, involving concerted CsH and CsO bond cleavage, were not found. The extent of substitution at the R-carbon on the alcohol was found to lead to marked effects on elimination barriers, because substitution increases the proton affinity of the alcohol and the stability of the carbenium-ion transition state. Changes in the central and addenda atoms of the POM cluster and the presence of n-donors, a support, vicinal POM clusters, or charge-compensating cations were found to lead to changes in the deprotonation energy (DPE) of the POM cluster, activation barriers to dehydration, and the stability of the unreactive dimer. These effects are all captured in a general linear relation between activation barriers and deprotonation energy, a rigorous measure of acid strength. The explicit dependence of the E1 activation barrier on the acid deprotonation energy is much weaker than that on reactant proton affinity. This results from the more effective compensation between the acid deprotonation energy and the interaction energy between the cationic hydrocarbon fragment and the anionic POM cluster at the transition state. The direct interactions between the POM protons and the support, other POM clusters, n-donors, base probe molecules, and charge-compensating cations increased the negative charge of the oxide shell of the W12O40 conjugate base, which increased the DPE and decreased the POM acid strength. This decrease in acidity is not fully compensated by the concomitant increase in the interaction energy, leading to elimination barriers that generally increase with increasing DPE.