AbstractIn supramolecular chemistry, the pursuit of highly efficient molecular recognition systems holds paramount significance. This study introduces new [2.2]paracyclophanes (PCP) as exceptional guest molecules for cucurbit[8]uril (CB8). This well‐matched host‐guest interaction is marked by ultra‐high binding affinities (K_a up to 10¹⁵ M⁻¹ in water) accompanied by unprecedented exothermic contributions (ΔH up to −20.6 kcal mol⁻¹) observed in CB8 binding, rivaling the exceptional affinities of cucurbit[7]uril (CB7), which has until now been recognized as the gold standard for high‐affinity binding in water. The PCPs demonstrate an excellent fit within the CB8 cavity without structural deformation of the host. Our research methodology incorporates organic synthesis, NMR, fluorescence titration, and isothermal titration calorimetry (ITC) experiments, as well as quantum mechanical simulations, to systematically examine the binding characteristics of fluorescent mono‐ and dicationic PCP guests within the CB8 cavity. This study not only corroborates but also critically reevaluates certain aspects of the “high‐energy water release model” for cucurbit[n]uril systems. Furthermore, the ease of modifying PCP compounds, combined with their superior water solubility compared to di‐ and triamantanes, and their characteristic fluorescent response in forming and disassembling host‐guest complexes, elevates PCPs as promising candidates for the creation of advanced supramolecular CB8‐functional materials and sensing assays.