A comprehensive thermodynamic study of the whole ortho-polyphenylbenzenes series from biphenyl (n = 1) to hexaphenylbenzene (n = 6) is presented. Combustion calorimetry and phase equilibria measurements for 1,2,3,4-tetraphenylbenzene (n = 4) and pentaphenylbenzene (n = 5) together with literature data were used to understand and quantify the constraint effect of ortho-substitution on the molecular energetics and phase stability of polyaromatic compounds. All of the derived thermodynamic properties (enthalpy of sublimation, entropy of sublimation, and gas phase molecular energetics) show a marked trend shift at n = 4 to 5, which is related to the change of the degree of molecular flexibility after 1,2,3,4-tetraphenylbenzene (n = 4). The greater intramolecular constraint in the more crowded members of the series (n = 5 and 6) leads to a significant change in the molecular properties and cohesive energy. The trend shift in the molecular properties is related with the decrease in molecular flexibility, which leads to lower molecular entropy and destabilization of the intramolecular interaction potential due to the increased hindrance in a confined molecular space.