We describe the syntheses of the tetra-α isomers of three unprecedented super aryl-extended calixpyrroles (SAE-CPs) functionalized with either eight carboxylic acids, eight pyridinium ions or eight 1-methyl-1H-imidazolium ions. The functional groups are located at the terminal positions of the four meso-aryl (upper rim) and four meso-alkyl (lower rim) substituents. The synthesized SAE-CPs are soluble in neutral or basic water solutions at mM concentrations. The cavity of the receptors is suitable for the inclusion of sizeable polar guests. We report the results of the binding studies of a series of pyridyl N-oxides, having a non-polar para-substituent, with the SAE-CP receptors in water using 1H NMR spectroscopy titrations and isothermal titration calorimetry (ITC) experiments. The receptors formed thermodynamically and kinetically stable 1 : 1 inclusion complexes with the N-oxide derivatives, featuring binding constant values larger than 105 M−1. We demonstrate the existence of linear relationships between the free energies of binding of the inclusion complexes and the surface area of the non-polar substituent of the guests. The slopes of the linear regressions provide quantitative values for the hydrophobic effect (33–38 cal mol−1 Å−2) in the binding of non-polar residues. The energy values derived for the hydrophobic effect using these simple host–guest systems are in line with those reported from studies of site-directed mutagenesis of protein residues and the transfer of solutes from non-polar solvents to water.