Aqueous solubilities of natural phenolic compounds from different families (hydroxyphenyl, polyphenol, hydroxybenzoic, and phenylpropenoic) were experimentally obtained. Measurements were performed on tyrosol and ellagic, protocatechuic, syringic, and o-coumaric acids, at five different temperatures (from 288.2 to 323.2 K), using the standard shake-flask method, followed by compositional analysis using UV spectrophotometry. To verify the accuracy of the spectrophotometric method, some data points were measured by gravimetry, and in general, the values obtained with the two methods are in good agreement (deviations lower than 11%). To adequately understand the solubilization process, melting properties of the pure phenolics were obtained by differential scanning calorimetry (DSC), and apparent acid dissociation constants were measured by potentiometry titration. The aqueous solubilities followed the expected general exponential trend. The melting temperatures did not follow the same solubility tendency, and for tyrosol and ellagic acid, not only the size and extent of hydrogen bonding, but also the energy associated with their crystal structures, determine the solubility. For these binary systems, acid dissociation is not important. Approaches for modeling the measured data were evaluated. These included an excess Gibbs energy equation, the modified UNIQUAC model, and the cubic-plus-association (CPA) equation of state. Particularly for the CPA approach, a new methodology that explicitly takes into account the number and nature of the associating sites and the prediction of the pure-component parameters from molecular structure is proposed. The results indicate that these are appropriate tools for representing the water solubilities of these molecules.